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1.
Discov Oncol ; 15(1): 220, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38858234

RESUMEN

Hepatocellular carcinoma (HCC) is a common primary liver cancer with a high incidence and mortality. Members of the growth-arresting-specific 2 (GAS2) family are involved in various biological processes in human malignancies. To date, there is only a limited amount of information available about the expression profile and clinical importance of GAS2 family in HCC. In this study, we found that GAS2L1 and GAS2L3 were distinctly upregulated in HCC specimens compared to non-tumor specimens. Pan-cancer assays indicated that GAS2L1 and GAS2L3 were highly expressed in most cancers. The Pearson's correlation revealed that the expressions of GAS2, GAS2L1 and GAS2L2 were negatively associated with methylation levels. Survival assays indicated that GAS2L1 and GAS2L3 were independent prognostic factors for HCC patients. Immune cell infiltration analysis revealed that GAS2, GAS2L1 and GAS2L3 were associated with several immune cells. Finally, we confirmed that GAS2L1 was highly expressed in HCC cells and its knockdown suppressed the proliferation of HCC cells. Taken together, our findings suggested the expression patterns and prognostic values of GAS2 members in HCC, providing insights for further study of the GAS2 family as sensitive diagnostic and prognostic markers for HCC.

2.
J Ethnopharmacol ; 330: 118223, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-38642624

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus japonicus Houtt. (Labiatae), commonly known as Chinese motherwort, is a herbaceous flowering plant that is native to Asia. It is widely acknowledged in traditional medicine for its diuretic, hypoglycemic, antiepileptic properties and neuroprotection. Currently, Leonurus japonicus (Leo) is included in the Pharmacopoeia of the People's Republic of China. Traditional Chinese Medicine (TCM) recognizes Leo for its myriad pharmacological attributes, but its efficacy against ICH-induced neuronal apoptosis is unclear. AIMS OF THE STUDY: This study aimed to identify the potential targets and regulatory mechanisms of Leo in alleviating neuronal apoptosis after ICH. MATERIALS AND METHODS: The study employed network pharmacology, UPLC-Q-TOF-MS technique, molecular docking, pharmacodynamic studies, western blotting, and immunofluorescence techniques to explore its potential mechanisms. RESULTS: Leo was found to assist hematoma absorption, thus improving the neurological outlook in an ICH mouse model. Importantly, molecular docking highlighted JAK as Leo's potential therapeutic target in ICH scenarios. Further experimental evidence demonstrated that Leo adjusts JAK1 and STAT1 phosphorylation, curbing Bax while augmenting Bcl-2 expression. CONCLUSION: Leo showcases potential in mitigating neuronal apoptosis post-ICH, predominantly via the JAK/STAT mechanism.


Asunto(s)
Apoptosis , Hemorragia Cerebral , Leonurus , Simulación del Acoplamiento Molecular , Farmacología en Red , Neuronas , Animales , Apoptosis/efectos de los fármacos , Leonurus/química , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Ratones , Masculino , Hemorragia Cerebral/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/aislamiento & purificación , Extractos Vegetales/farmacología , Extractos Vegetales/química , Janus Quinasa 1/metabolismo , Factor de Transcripción STAT1/metabolismo , Modelos Animales de Enfermedad
3.
J Integr Med ; 22(3): 258-269, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38677968

RESUMEN

Urinary incontinence (UI) is a common problem worldwide. It has a major impact on physical and social activities and interpersonal relationships. UI is common in women, but is under-reported and under-treated. It affects the quality of life of female patients severely. Acupuncture and moxibustion have been proposed as potentially effective interventions for female UI. Hence, for the benefit of acupuncture practitioners around the world, the World Federation of Acupuncture-moxibustion Societies initiated a project to develop a clinical practice guideline (CPG) for the use of acupuncture and moxibustion to treat female UI. This CPG was developed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, referring to the principles of the World Health Organization Handbook for Guideline Development. During the development of the CPG, the guideline development group (GDG) played an important role. The clinical questions, recommendations and therapeutic protocols were all formulated by GDG using the modified Delphi method. This CPG contains ten recommendations about the use of acupuncture and moxibustion interventions for ten clinical questions, which include nine conditional recommendations for the intervention and one conditional recommendation for either the intervention or the comparison. This CPG also provides one protocol for conventional filiform needle therapy, two therapy protocols for deep needling stimulation on lumbosacral acupoints, and four moxibustion therapy protocols, based on the protocols presented in randomized controlled trials reviewed by the GDG. Please cite this article as: Yang C, Wang SZ, Chen S, Du S, Wang GQ, Guo W, Xie XL, Peng BH, Du SH, Zhao JP. Clinical practice guideline for acupuncture and moxibustion: Female urinary incontinence. J Integr Med. 2024; 22(3): 258-269.


Asunto(s)
Terapia por Acupuntura , Moxibustión , Incontinencia Urinaria , Humanos , Femenino , Incontinencia Urinaria/terapia , Guías de Práctica Clínica como Asunto
4.
J Integr Med ; 22(3): 245-257, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38616445

RESUMEN

Acupuncture is one of the most effective complementary therapies for allergic rhinitis (AR) and has been recommended by several clinical practice guidelines (CPGs) for AR. However, these CPGs mentioned acupuncture without making recommendations for clinical implementation and therapeutic protocols, therefore limiting the applicability of acupuncture therapies for AR. Hence, for the benefit of acupuncture practitioners around the world, the World Federation of Acupuncture-moxibustion Societies have initiated a project to develop the CPG for the use of acupuncture and moxibustion to treat AR. This CPG was developed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, referring to the principles of the World Health Organization Handbook for Guideline Development. During the development of the CPG, the guideline development group (GDG) played an important role. The clinical questions, recommendations and therapeutic protocols were all formulated by the GDG using the modified Delphi method. The CPG contains recommendations for 15 clinical questions about the use of acupuncture and moxibustion interventions. These include one strong recommendation for the intervention based on high-quality evidence, three conditional recommendations for either the intervention or standard care, and 11 conditional recommendations for the intervention based on very low quality of evidence. The CPG also provides one filiform needle acupuncture protocol and five moxibustion protocols extracted based on the protocols presented in randomized controlled trials reviewed by the GDG. Please cite this article as: Du SH, Chen S, Wang SZ, Wang GQ, Du S, Guo W, Xie XL, Peng BH, Yang C, Zhao JP. Clinical practice guideline for acupuncture and moxibustion: Allergic rhinitis. J Integr Med. 2024; 22(3): 245-257.


Asunto(s)
Terapia por Acupuntura , Moxibustión , Rinitis Alérgica , Humanos , Rinitis Alérgica/terapia , Guías de Práctica Clínica como Asunto
5.
Cells ; 13(7)2024 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-38607007

RESUMEN

Solid tumors, with their intricate cellular architecture and genetic heterogeneity, have long posed therapeutic challenges. The advent of the CRISPR genome editing system offers a promising, precise genetic intervention. However, the journey from bench to bedside is fraught with hurdles, chief among them being the efficient delivery of CRISPR components to tumor cells. Lipid nanoparticles (LNPs) have emerged as a potential solution. This biocompatible nanomaterial can encapsulate the CRISPR/Cas9 system, ensuring targeted delivery while mitigating off-target effects. Pre-clinical investigations underscore the efficacy of LNP-mediated CRISPR delivery, with marked disruption of oncogenic pathways and subsequent tumor regression. Overall, CRISPR/Cas9 technology, when combined with LNPs, presents a groundbreaking approach to cancer therapy, offering precision, efficacy, and potential solutions to current limitations. While further research and clinical testing are required, the future of personalized cancer treatment based on CRISPR/Cas9 holds immense promise.


Asunto(s)
Nanoestructuras , Neoplasias , Humanos , Sistemas CRISPR-Cas/genética , Edición Génica , Terapia Genética , Neoplasias/genética , Neoplasias/terapia
6.
Artículo en Inglés | MEDLINE | ID: mdl-38607191

RESUMEN

Background: Repeated episodes of jaundice and pruritus are common in a group of autosomal recessive liver diseases known as benign recurrent intrahepatic cholestasis. Benign recurrent intrahepatic cholestasis (BRIC) is divided into two types, type 1 and type 2, and is caused by mutations in the ATP8B1 and ABCB11 genes. Here, we report a rare case of BRIC type 2 mutation. Case presentation: A 45-year-old Chinese man had three frequent episodes of jaundice marked by extensive excoriation and severe pruritis, although he had no prior history of jaundice. Laboratory investigations showed no evidence of liver damage caused by viral, autoimmune, or acquired metabolic etiologies. The CT scan revealed an enlarged gallbladder with numerous punctate high-density shadows, while no wall thickening was observed. Endoscopic ultrasonography showed no evidence of dilation of the intrahepatic and extrahepatic bile duct, as well as the absence of gallstone. Diagnostic evaluation: Immunohistochemical examinations of liver biopsy samples showed cytokeratin-7 positive hepatocytes, suggesting chronic intrahepatic cholestasis. The reticulin fiberstaining demonstrated that the portions of the hepatic plate in the center of the lobule were asymmetrically organized,and somewhat enlarged, with collapsed areas indicating intralobular inflammation. Moreover, there were areas of collapse that indicated the presence of intralobular inflammation. Whole exome sequencing revealed mutations in the ABCB11 gene; c.3084A>G, p.A1028A homozygous mutation (chr2-169789016), and c.2594C>T, p.A865V heterozygous mutation (chr2-169801131). Based on these findings, the final diagnosis of the patient was metabolism-related jaundice. Treatment: Apart from receiving tapering dosage of prednisone to lower bilirubin levels, the patient received no extra care. Conclusion: The comprehensive diagnosis of a middle-aged male patient with BRIC-2, which involved extensive radiological, hematological, and genetic investigations, informed a tailored tapering prednisone regimen, highlighting the importance of personalized medicine in managing atypical presentations of this rare cholestatic disorder.

7.
iScience ; 27(3): 109160, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38414861

RESUMEN

Neoadjuvant chemotherapy (NACT) is a therapeutic option for locally advanced cervical cancer (LACC) patients. This study was aimed to identify potential liquid biopsy biomarkers to monitor the NACT response. Through targeted next-generation sequencing (NGS) analysis of circulating tumor DNA (ctDNA) and tumor tissue DNA (ttDNA) taken from LACC patients undergoing platinum-based NACT, 64 genes with mutations emerge during NACT in the non-responders but none in the responders. Among them, the PBRM1, SETD2, and ROS1 mutations were frequently detected in the ctDNA and ttDNA of the non-responders, and mutant PBRM1 was associated with poorer survival of patients. In vitro, PBRM1 knockdown promoted resistance to cisplatin through boosting STAT3 signaling in cervical cancer cells, while it sensitized tumor cells to poly-ADP-ribose-polymerase inhibitor olaparib. These findings suggest that mutant PBRM1 is a potential ctDNA marker of emerging resistance to NACT and of increased sensitivity to olaparib, which warrants further clinical validation.

8.
Phytomedicine ; 125: 155342, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38295665

RESUMEN

BACKGROUND: Type 2 diabetes is often linked with osteoporosis (T2DOP), a condition that accelerates bone degeneration and increases the risk of fractures. Unlike conventional menopausal osteoporosis, the diabetic milieu exacerbates the likelihood of fractures and osteonecrosis. In particular poliumoside (Pol), derived from Callicarpa kwangtungensis Chun, has shown promising anti-oxidant and anti-inflammatory effects. Yet, its influence on T2DOP remains to be elucidated. PURPOSE: The focus of this study was to elucidate the influence of Pol in HGHF-associated ferroptosis and its implications in T2DOP. STUDY DESIGN: A murine model of T2DOP was established using a minimal dosage of streptozotocin (STZ) through intraperitoneal infusion combined with a diet high in fat and sugar. Concurrently, to mimic the diabetic condition in a lab environment, bone mesenchymal stem cells (BMSCs) were maintained in a high-glucose and high-fat (HGHF) setting. METHODS: The impact of Pol on BMSCs in an HGHF setting was determined using methods, such as BODIPY-C11, FerroOrange staining, mitochondrial functionality evaluations, and Western blot methodologies, coupled with immunoblotting and immunofluorescence techniques. To understand the role of Pol in a murine T2DOP model, techniques including micro-CT, hematoxylin and eosin (H&E) staining, dual-labeling with calcein-alizarin red, and immunohistochemistry were employed for detailed imaging and histological insights. RESULTS: Our findings suggest that Pol acts against HGHF-induced bone degradation and ferroptosis, as evidenced by an elevation in glutathione (GSH) and a decline in malondialdehyde (MDA) levels, lipid peroxidation, and mitochondrial reactive oxygen species (ROS). Furthermore, Pol treatment led to increased bone density, enhanced GPX4 markers, and reduced ROS in the distal femur region. On investigating the underlying mechanism of action, it was observed that Pol triggers the Nrf2/GPX4 pathway, and the introduction of lentivirus-Nrf2 negates the beneficial effects of Pol in HGHF-treated BMSCs. CONCLUSION: Pol is effective in treating T2DOP by activating the Nrf2/GPX4 signaling pathway to inhibit ferroptosis.


Asunto(s)
Ácidos Cafeicos , Diabetes Mellitus Tipo 2 , Ferroptosis , Glicósidos , Osteoporosis , Animales , Ratones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Factor 2 Relacionado con NF-E2 , Especies Reactivas de Oxígeno , Osteoporosis/tratamiento farmacológico , Osteoporosis/prevención & control
9.
Nat Commun ; 15(1): 739, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38272900

RESUMEN

Adipose stem cells (ASCs) have attracted considerable attention as potential therapeutic agents due to their ability to promote tissue regeneration. However, their limited tissue repair capability has posed a challenge in achieving optimal therapeutic outcomes. Herein, we conceive a series of lipid nanoparticles to reprogram ASCs with durable protein secretion capacity for enhanced tissue engineering and regeneration. In vitro studies identify that the isomannide-derived lipid nanoparticles (DIM1T LNP) efficiently deliver RNAs to ASCs. Co-delivery of self-amplifying RNA (saRNA) and E3 mRNA complex (the combination of saRNA and E3 mRNA is named SEC) using DIM1T LNP modulates host immune responses against saRNAs and facilitates the durable production of proteins of interest in ASCs. The DIM1T LNP-SEC engineered ASCs (DS-ASCs) prolong expression of hepatocyte growth factor (HGF) and C-X-C motif chemokine ligand 12 (CXCL12), which show superior wound healing efficacy over their wild-type and DIM1T LNP-mRNA counterparts in the diabetic cutaneous wound model. Overall, this work suggests LNPs as an effective platform to engineer ASCs with enhanced protein generation ability, expediting the development of ASCs-based cell therapies.


Asunto(s)
Tejido Adiposo , Diabetes Mellitus , Humanos , Tejido Adiposo/metabolismo , ARN/metabolismo , Cicatrización de Heridas/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Células Madre/metabolismo , Diabetes Mellitus/metabolismo
10.
Int Immunopharmacol ; 128: 111469, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38211480

RESUMEN

Osteoarthritis (OA) is a prevalent joint disorder pathologically correlated to chondrocyte ferroptosis. Gamma-oryzanol (γ-Ory), as a first-line drug for autonomic disorders, aroused our interest because of its antioxidant, lipid-lowering, and hypoglycemic potential. The purpose of this study was to investigate the potential impact and mechanism of γ-Ory in treating OA. And the inhibition of γ-Ory in extracellular matrix molecule (ECM) degradation, ferroptosis, and Keap1-Nrf2 binding in IL-1ß-exposed chondrocytes was detected via immunoblotting, immunofluorescence, and co-immunoprecipitation. Micro-CT, SO staining, and immunofluorescence have been conducted to assess the impact of γ-Ory treatment on ACLT-mediated OA in rats at both imaging and histological stages. We found that γ-Ory dose-dependently suppressed IL-1ß-induced ECM deterioration and chondrocyte ferroptosis. Our animal experiments revealed that γ-Ory delayed ACLT-mediated OA development. Mechanistically, γ-Ory interfered with the binding of Keap1 to Nrf2 to promote the latter's nuclear import, thereby increasing the expression of detoxification enzymes. Summarily, our works support γ-Ory's potential as a candidate drug for the treatment of OA.


Asunto(s)
Ferroptosis , Osteoartritis , Fenilpropionatos , Animales , Ratas , Condrocitos/metabolismo , Interleucina-1beta/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Osteoartritis/tratamiento farmacológico , Fenilpropionatos/uso terapéutico
11.
Zhongguo Zhen Jiu ; 43(12): 1449-1453, 2023 Dec 12.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-38092548

RESUMEN

Taking the recommendations development of the World Federation of Acupuncture-Moxibustion Societies (WFAS) standard Clinical Practice Guideline for Female Urinary Incontinence as an example, this study analyzed the consensus expert composition, specific consensus process, and results in the development of the guideline's recommendations. It systematically examined the advantages of using the modified Delphi method in the formation of recommendations for acupuncture and moxibustion clinical practice guideline, with the aim of providing reference for the development of acupuncture and moxibustion guidelines in the same field.


Asunto(s)
Terapia por Acupuntura , Acupuntura , Moxibustión , Femenino , Humanos , Técnica Delphi
12.
Exp Biol Med (Maywood) ; 248(23): 2408-2420, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38158612

RESUMEN

Renal ischemia-reperfusion injury (IRI) is a common clinical complication of multiple severe diseases. Owing to its high mortality and the lack of effective treatment, renal IRI is still an intractable problem for clinicians. Itaconate, which is a metabolite of cis-aconitate, can exert anti-inflammatory and antioxidant roles in many diseases. As a derivative of itaconate with high cell membrane permeability, 4-octyl itaconate (4-OI) could provide a protective effect for various diseases. However, the role of 4-OI in renal IRI is still unclear. Herein, we examined whether 4-OI afforded kidney protection through attenuating endoplasmic reticulum stress (ERS) via nuclear factor erythroid-2-related factor 2 (Nrf2) pathway. To observe the effects of 4-OI on alleviating renal pathologic injury, improving renal dysfunction, decreasing inflammatory cytokines, and reducing oxidative stress, we utilized C57BL/6J mice with bilateral renal pedicle clamped and HK-2 cells with hypoxia/reoxygenation (H/R) exposure in our study. In addition, through western blot assay, we found 4-OI ameliorated renal IRI-induced ERS, and activated Nrf2 pathway. Moreover, Nrf2-knockout (KO) mice and Nrf2 knockdown HK-2 cells were used to validate the role of Nrf2 signaling pathway in 4-OI-mediated alleviation of ERS caused by renal IRI. We demonstrated that 4-OI relieved renal injury and suppressed ERS in wild-type mice, while the therapeutic role was not shown in Nrf2-KO mice. Similarly, 4-OI could exert cytoprotective effect and inhibit ERS in HK-2 cells after H/R, but not in Nrf2 knockdown cells. Our in vivo and in vitro studies revealed that 4-OI protected renal IRI through attenuating ERS via Nrf2 pathway.


Asunto(s)
Factor 2 Relacionado con NF-E2 , Daño por Reperfusión , Succinatos , Ratones , Animales , Factor 2 Relacionado con NF-E2/metabolismo , Ratones Endogámicos C57BL , Riñón/patología , Estrés Oxidativo , Daño por Reperfusión/metabolismo , Estrés del Retículo Endoplásmico , Apoptosis
13.
World J Gastrointest Oncol ; 15(10): 1706-1716, 2023 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-37969410

RESUMEN

Inositol polyphosphate-4-phosphatase type II (INPP4B) is a newly discovered PI(3,4,5)P3 phosphatase. Many studies have revealed that INPP4B is upregulated or downregulated in tumors of the digestive system, and the abnormal expression of INPP4B may be attributed to the occurrence, development, and prognosis of tumors of the digestive system. This paper reviews studies on the correlations between INPP4B and digestive system tumors and the roles of INPP4B in the development of different tumors to provide a theoretical basis for further research on its molecular mechanism and clinical application. "INPP4B" and "tumor" were searched as key words in PubMed and in the CNKI series full text database retrieval system from January 2000 to August 2023. A total of 153 English-language studies and 30 Chinese-language studies were retrieved. The following enrollment criteria were applied: (1) Studies contained information on the biological structure and functions of INPP4B; (2) studies covered the influence of abnormal expression of INPP4B in digestive system tumors; and (3) studies covered the role of INPP4B in the diagnosis, treatment, and prognosis of digestive system tumors. After excluding the literature irrelevant to this study, 61 papers were finally included in the analysis. INPP4B expression is low in gastric cancer, colon cancer, pancreatic cancer, and liver cancer but it has high expression in esophageal cancer, colon cancer, pancreatic cancer, and gallbladder cancer. INPP4B is involved in the occurrence and development of digestive system tumors through the regulation of gene expression and signal transduction. The abnormal expression of INPP4B plays an important role in the development of digestive system tumors. Studies on INPP4B provide new molecular insights for the diagnosis, treatment, and prognosis evaluation of digestive system tumors.

14.
Exploration (Beijing) ; 3(4): 20210058, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37933232

RESUMEN

Adoptive cell therapy (ACT) is a rapidly growing anti-cancer strategy that has shown promise in treating various cancer types. The concept of ACT involves activating patients' own immune cells ex vivo and then transferring them back to the patients to recognize and eliminate cancer cells. Currently, the commonly used ACT includes tumor-infiltrating lymphocytes (TILs), genetically engineered immune cells, and dendritic cells (DCs) vaccines. With the advancement of cell culture and genetic engineering techniques, ACT has been used in clinics to treat malignant hematological diseases and many new ACT-based regimens are in different stages of clinical trials. Here, representative ACT approaches are introduced and the opportunities and challenges for clinical translation of ACT are discussed.

15.
J Agric Food Chem ; 2023 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-37917162

RESUMEN

Osteoporosis (OP) is typically brought on by disruption of bone homeostasis. Excessive oxidative stress and mitochondrial dysfunction are believed to be the primary mechanisms underlying this disorder. Therefore, in order to restore bone homeostasis effectively, targeted treatment of oxidative stress and mitochondrial dysfunction is necessary. Cinnamaldehyde (CIN), a small molecule that acts as an agonist for the nuclear factor erythroid 2-related factor (Nrf2), has been found to possess antiapoptotic, anti-inflammatory, and antioxidant properties. We found that CIN, while rescuing apoptosis, can also reduce the accumulation of reactive oxygen species (ROS) to improve mitochondrial dysfunction and thus restore the osteogenic differentiation potential of BMSCs disrupted by hydrogen peroxide (H2O2) exposure. The role of CIN was preliminarily considered to be a consequence of Nrf2/HO-1 axis activation. The ovariectomized mice model further demonstrated that CIN treatment ameliorated oxidative stress in vivo, partially reversing OVX-induced bone loss. This improvement was seen in the trabecular microarchitecture and bone biochemical indices. However, when ML385 was concurrently injected with CIN, the positive effects of CIN were largely blocked. In conclusion, this study sheds light on the intrinsic mechanisms by which CIN regulates BMSCs and highlights the potential therapeutic applications of these findings in the treatment of osteoporosis.

16.
Cancer Lett ; 578: 216460, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37863352

RESUMEN

Coiled-Coil Domain-Containing (CCDC) is a large class of structural proteins containing left-handed supercoiled structure. The clinical value and the functional implication of CCDC in colorectal cancer (CRC) remain unknown. Based on the genetic, transcriptional, and clinical data from The Cancer Genome Atlas, five of thirty-six CCDC proteins were differentially expressed in the CRC and associated with the survival of patients with CRC. A CCDC-score model was established to evaluate the prognosis of patients. The potential function of Coiled-Coil Domain-Containing 154 (CCDC154) was investigated using bioinformatical methods, which unveiled that high expression of CCDC154 indicates poor survival for patients with CRC and correlates with low infiltration of CD8+ T cells and high infiltration of neutrophils, indicating that CCDC154 enhances tumor growth and metastasis. CCDC154 interacts with Minichromosome Maintenance Complex Component 2 (MCM2) protein and promotes malignant phenotype via MCM2. We validated the expression level and survival prediction value of CCDC154 in clinical samples, and analyzed its co-expression of MCM2, Ki-67 and p53. This work discloses the role of CCDC in clinical setting and CCDC154 functions in CRC.


Asunto(s)
Proteínas de Ciclo Celular , Neoplasias Colorrectales , Humanos , Linfocitos T CD8-positivos/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proliferación Celular , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Componente 2 del Complejo de Mantenimiento de Minicromosoma/genética , Componente 2 del Complejo de Mantenimiento de Minicromosoma/metabolismo , Pronóstico
17.
J Phys Condens Matter ; 36(5)2023 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-37871601

RESUMEN

Copper selenide (Cu2Se) has attracted significant attention due to the extensive applications in thermoelectric and optoelectronic devices over the last few decades. Among various phase structures of Cu2Se, layered Cu2Se exhibits unique properties, such as purely thermal phase transition, high carrier mobility, high optical absorbance and high photoconductivity. Herein, we carry out a systematic investigation for the electronic structures of layered Cu2Se with several exchange-correlation functionals at different levels through first-principle calculations. It can be found that the electronic structures of layered Cu2Se are highly sensitive to the choice of functionals, and the correction of on-site Coulomb interaction also has a noticeable influence. Comparing with the results calculated with hybrid functional and G0W0method, it is found that the electronic structures calculated with LDA +Ufunctional are relatively accurate for layered Cu2Se. In addition, the in-plane biaxial strain can lead to the transition of electronic properties from metal to semiconductor in the layered Cu2Se, attributed to the change of atomic orbital hybridization. Furthermore, we explore the spin-orbit coupling (SOC) effect of Cu2Se and find that the weak SOC effect on electronic structures mainly results from spatial inversion symmetry of Cu2Se. These findings provide valuable insights for further investigation on this compound.

18.
J Control Release ; 362: 396-408, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37657692

RESUMEN

Tumor recurrence mainly triggered by tumor residual cells significantly contributes to mortality following breast tumor resection, and meanwhile post-surgical bacterial wound infections may accelerate tumor recurrence due to a series of infection-related complications. In this study, a nano-sensor system, Van-ICG@PLT, is constructed by a membrane camouflage and small molecule drug self-assembly strategy. This nano-sensor harnesses the innate tropism of platelets (PLT) to deliver vancomycin (Van) and indocyanine green (ICG) to surgical incisions, effectively eliminating both residual tumor cells and bacterial infections. Our findings demonstrate that Van-ICG@PLT preferentially accumulates at surgical wound. Under near-infrared (NIR) laser irradiation, Van-ICG@PLT exhibits significant cytotoxicity against 4T1 cells. Additionally, it is found to significantly promote ROS production thus inhibiting Staphylococcus aureus (S. aureus) growth, underscoring the synergistic benefits of phototherapy in combination with antibiotic treatment. In the 4T1 post-surgery recurrence mice model, Van-ICG@PLT is shown to efficiently ablate tumors in tumor-bearing mice (tumor inhibition rate of about 83%), and it demonstrates an excellent anti-infective effect in mice abscess models. Taken together, Van-ICG@PLT represents a promising paradigm in post-surgical adjuvant therapy (PAT). Its dual benefit in inhibiting cancer growth and promoting antibacterial activity makes Van-ICG@PLT a valuable addition to the existing arsenal of therapeutic options available for breast cancer patients.

19.
Support Care Cancer ; 31(9): 508, 2023 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-37548752

RESUMEN

OBJECTIVE: The goal of this research was to review the literature from randomized controlled trials (RCTs) on the impacts of moxibustion on cancer-related fatigue (CRF) as well as provide credible evidence to guide clinical practice. METHODS: Three English electronic medical databases (PubMed, Embase, and the Cochrane Library) and two Chinese databases (China National Knowledge Infrastructure and Wanfang) were searched. Only randomized controlled trials on the effect of moxibustion on CRF were included in this systematic review. Study selection, data extraction, and validation were all carried out independently by two reviewers. The revised Cochrane Risk of Bias tool was used to assess the quality of the RCTs (RoB 2.0). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was applied to assess effect sizes in individual RCTs and pooled effect sizes in meta-analyses. Data were meta-analyzed using Stata (version 14.0). RESULTS: In a random-effects meta-analysis of 24 RCTs with 1894 participants, the aggregated standardized mean difference (SMD) revealed a statistically significant association between moxibustion and alleviation from cancer-related fatigue (SMD = - 1.66, 95% CI = - 2.05, - 1.28, p = 0.000). Pooled results, however, show significant heterogeneity (I2 = 92.5%), and the evidence is insufficient to determine whether this association varies systematically by measuring tools and moxibustion modalities. Furthermore, evidence ranging from very low to low showed that moxibustion had an immediate positive effect on patients with CRF. CONCLUSION: Moxibustion may have a therapeutic effect on cancer-related fatigue. However, further large-scale, multicenter, high-quality RCTs on moxibustion for fatigue relief and safety are still needed because of the handful of studies included and the low methodological quality.


Asunto(s)
Moxibustión , Neoplasias , Humanos , China , Fatiga/etiología , Fatiga/terapia , Estudios Multicéntricos como Asunto , Neoplasias/complicaciones , Neoplasias/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto
20.
World J Gastroenterol ; 29(24): 3871-3882, 2023 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-37426321

RESUMEN

BACKGROUND: Stereotactic body radiotherapy (SBRT) and programmed cell death 1 inhibitors have shown potential in treating hepatocellular carcinoma (HCC) in retrospective studies. AIM: To evaluate the efficacy of combining SBRT with sintilimab for patients with recurrent or oligometastatic HCC. METHODS: This trial involved patients with recurrent or oligometastatic HCC intravenously treated with SBRT plus sintilimab every 3 wk for 12 mo or until disease progression. The primary endpoint was progression-free survival (PFS). RESULTS: Twenty-five patients were enrolled from August 14, 2019, to August 23, 2021. The median treatment duration was 10.2 (range, 0.7-14.6) months. SBRT was delivered at a median dose of 54 (range, 48-60) Gy in 6 (range, 6-10) fractions. The median follow-up time was 21.9 (range, 10.3-39.7) mo, and 32 targeted lesions among 25 patients were evaluated for treatment response according to the Response Evaluation Criteria in Solid Tumors version 1.1. The median PFS was 19.7 mo [95% confidence interval (CI): 16.9-NA], with PFS rates of 68% (95%CI: 52-89) and 45.3% (95%CI: 28-73.4) at 12 and 24 mo, respectively. The median overall survival (OS) was not reached, with OS rates of 91.5% (95%CI: 80.8-100.0) and 83.2% (95%CI: 66.5-100.0) at 12 and 24 mo, respectively. The 1- and 2-year local control rate were 100% and 90.9% (95%CI: 75.4%-100.0%), respectively. The confirmed objective response rate and disease control rate was 96%, and 96%, respectively. Most adverse events were graded as 1 or 2, and grade 3 adverse events were observed in three patients. CONCLUSION: SBRT plus sintilimab is an effective, well-tolerated treatment regimen for patients with recurrent or oligometastatic HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Radiocirugia , Humanos , Radiocirugia/efectos adversos , Estudios Retrospectivos
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