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1.
Int Wound J ; 21(4): e14886, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38651532

RESUMO

Negative pressure injury is one of the auxiliary methods of treating diabetes foot ulcers. It has been shown to be superior to conventional techniques in randomized controlled trials (RCTs). Nevertheless, the results of observational research are still scarce. A systematic review of RCTs and observations was carried out to evaluate the effectiveness and security of negative pressure wound therapy (NPWT) treatment for diabetes foot ulcers. Three English e-databases have been found for NPWT research. The meta-analyses of the comparative studies provided point estimates of results. Intermediate results were given as median and binary values were given in the form of odds ratios (OR). Seventeen trials, 13 RCTs and four randomized, controlled trials were found in the survey. Of these, 831 were treated with NPWT, 834 were treated with standard therapy. A total of 14 studies have been conducted to investigate the influence of NPWT on the healing of diabetic foot ulcers(DFU). In the study, NPWT was shown to speed up the healing of the wound in DFU patients(OR, 2.57; 95% CI, 1.72, 3.85 p < 0.0001). A subgroup analysis showed that NPWT was associated with an acceleration of the wound healing rate in 10 RCT trials (OR, 2.48; 95% CI, 1.58, 3.89 p < 0.001). In the four nRCT trials, NPWT was also shown to speed up the healing of the wound(OR, 2.95; 95% CI, 1.03, 8.42 p = 0.04). In 11 studies, the influence of NPWT on amputations of diabetes mellitus (DM) foot ulcers was investigated. The results showed that NPWT was associated with a reduction in amputations (OR, 0.53; 95% CI, 0.37, 0.74 p = 0.0002).In a subgroup of RCT trials, nine RCT trials showed a reduction in amputations(OR, 0.61; 95% CI, 0.43, 0.87 p = 0.007). In both nRCT trials, NPWT also showed a reduction in amputations (OR, 0.03; 95% CI, 0.00, 0.24 p = 0.001). Generally speaking, NPWT can help to heal the wound and lower the risk of amputations in people with diabetes. The subgroup analysis showed similar results for the RCT and non-RCT trials. NPWT can be used to treat diabetes foot ulcers caused by diabetes.

2.
Small ; : e2309882, 2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38342670

RESUMO

Negative therapeutic feedback of inflammation would extensively attenuate the antitumor effect of photodynamic therapy (PDT). In this work, tumor homing chimeric peptide rhomboids (designated as NP-Mel) are fabricated to improve photodynamic performance by inhibiting PDT-upregulated cyclooxygenase-2 (COX-2). The hydrophobic photosensitizer of protoporphyrin IX (PpIX) and palmitic acid are conjugated onto the neuropilin receptors (NRPs) targeting peptide motif (CGNKRTR) to obtain tumor homing chimeric peptide (Palmitic-K(PpIX)CGNKRTR), which can encapsulate the COX-2 inhibitor of meloxicam. The well dispersed NP-Mel not only improves the drug stability and reactive oxygen species (ROS) production ability, but also increase the breast cancer targeted drug delivery to intensify the PDT effect. In vitro and in vivo studies verify that NP-Mel will decrease the secretion of prostaglandin E2 (PGE2) after PDT treatment, inducing the downregulation of IL-6 and TNF-α expressions to suppress PDT induced inflammation. Ultimately, an improved PDT performance of NP-Mel is achieved without inducing obvious systemic toxicity, which might inspire the development of sophisticated nanomedicine in consideration of the feedback induced therapeutic resistance.

3.
J Neurosci Res ; 102(1): e25283, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38284859

RESUMO

Spinal cord injury (SCI) is a highly disabling neurological disorder that is difficult to treat due to its complex pathophysiology and nerve regeneration difficulties. Hence, effective SCI treatments are necessary. Olfactory ensheathing cells (OECs), glial cells derived from the olfactory bulb or mucosa, are ideal candidates for SCI treatment because of their neuroprotective and regenerative properties, ample supply, and convenience. In vitro, animal model, and human trial studies have reported discoveries on OEC transplantation; however, shortcomings have also been demonstrated. Recent studies have optimized various OEC transplantation strategies, including drug integration, biomaterials, and gene editing. This review aims to introduce OECs mechanisms in repairing SCI, summarize the research progress of OEC transplantation-optimized strategies, and provide novel research ideas for SCI treatment.


Assuntos
Edição de Genes , Traumatismos da Medula Espinal , Animais , Humanos , Regeneração Nervosa , Neuroglia , Neuroproteção , Traumatismos da Medula Espinal/terapia
4.
Biosensors (Basel) ; 14(1)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38275310

RESUMO

Carcinoembryonic antigen (CEACAM5), as a broad-spectrum tumor biomarker, plays a crucial role in analyzing the therapeutic efficacy and progression of cancer. Herein, we propose a novel biosensor based on specklegrams of tapered multimode fiber (MMF) and two-dimensional convolutional neural networks (2D-CNNs) for the detection of CEACAM5. The microfiber is modified with CEA antibodies to specifically recognize antigens. The biosensor utilizes the interference effect of tapered MMF to generate highly sensitive specklegrams in response to different CEACAM5 concentrations. A zero mean normalized cross-correlation (ZNCC) function is explored to calculate the image matching degree of the specklegrams. Profiting from the extremely high detection limit of the speckle sensor, variations in the specklegrams of antibody concentrations from 1 to 1000 ng/mL are measured in the experiment. The surface sensitivity of the biosensor is 0.0012 (ng/mL)-1 within a range of 1 to 50 ng/mL. Moreover, a 2D-CNN was introduced to solve the problem of nonlinear detection surface sensitivity variation in a large dynamic range, and in the search for image features to improve evaluation accuracy, achieving more accurate CEACAM5 monitoring, with a maximum detection error of 0.358%. The proposed fiber specklegram biosensing scheme is easy to implement and has great potential in analyzing the postoperative condition of patients.


Assuntos
Técnicas Biossensoriais , Neoplasias , Humanos , Antígeno Carcinoembrionário , Proteínas Ligadas por GPI
5.
Tissue Eng Regen Med ; 21(2): 277-290, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37947984

RESUMO

BACKGROUND: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a severe congenital disorder characterized by vaginal hypoplasia caused by dysplasia of the Müllerian duct. Patients with MRKH syndrome often require nonsurgical or surgical treatment to achieve satisfactory vaginal length and sexual outcomes. The extracellular matrix has been successfully used for vaginal reconstruction. METHODS: In this study, we developed a new biological material derived from porcine vagina (acellular vaginal matrix, AVM) to reconstruct the vagina in Bama miniature pigs. The histological characteristics and efficacy of acellularization of AVM were evaluated, and AVM was subsequently transplanted into Bama miniature pigs to reconstruct the vaginas. RESULTS: Macroscopic analysis showed that the neovaginas functioned well in all Bama miniature pigs with AVM implants. Histological analysis and electrophysiological evidence indicated that morphological and functional recovery was restored in normal vaginal tissues. Scanning electron microscopy showed that the neovaginas had mucosal folds characteristics of normal vagina. No significant differences were observed in the expression of CK14, HSP47, and α-actin between the neovaginas and normal vaginal tissues. However, the expression of estrogen receptor (ER) was significantly lower in the neovaginas than in normal vaginal tissues. In addition, AVM promoted the expression of ß-catenin, c-Myc, and cyclin D1. These results suggest that AVM might promotes vaginal regeneration by activating the ß-catenin/c-Myc/cyclin D1 pathway. CONCLUSION: This study reveals that porcine-derived AVM has potential application for vaginal regeneration.


Assuntos
Transtornos 46, XX do Desenvolvimento Sexual , Anormalidades Congênitas , Ciclina D1 , Ductos Paramesonéfricos/anormalidades , Engenharia Tecidual , Humanos , Feminino , Suínos , Animais , beta Catenina , Porco Miniatura , Vagina/anormalidades , Vagina/cirurgia
6.
Small ; : e2309994, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38095445

RESUMO

A systemic treatment strategy is urgently demanded to suppress the rapid growth and easy metastasis characteristics of breast cancer. In this work, a chimeric peptide-engineered self-delivery nanomedicine (designated as ChiP-CeR) for photodynamic-triggered breast cancer immunotherapy by macrophage polarization. Among these, ChiP-CeR is composed of the photosensitizer of chlorine e6 (Ce6) and the TLR7/8 agonist of lmiquimod (R837), which is further modified with tumor matrix targeting peptide (Fmoc-K(Fmoc)-PEG8 -CREKA. ChiP-CeR is preferred to actively accumulate at the tumor site via specific recognition of fibronectin, which can eradicate primary tumor growth through photodynamic therapy (PDT). Meanwhile, the destruction of primary tumors would trigger immunogenic cell death (ICD) effects to release high-mobility group box-1(HMGB1) and expose calreticulin (CRT). Moreover, ChiP-CeR can also polarize M2-type tumor-associated macrophages (TAMs) into M1-type TAMs, which can activate T cell antitumor immunity in combination with ICD. Overall, ChiP-CeR possesses superior antitumor effects against primary and lung metastatic tumors, which provide an applicable nanomedicine and a feasible strategy for the systemic management of metastatic breast cancer.

7.
BMC Anesthesiol ; 23(1): 366, 2023 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-37946114

RESUMO

The latest clinical trials have reported conflicting outcomes regarding the effectiveness of xenon anesthesia in preventing postoperative neurocognitive dysfunction; thus, this study assessed the existing evidence. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases from inception to April 9, 2023, for randomized controlled trials of xenon anesthesia in postoperative patients. We included English-language randomized controlled studies of adult patients undergoing surgery with xenon anesthesia that compared its effects to those of other anesthetics. Duplicate studies, pediatric studies, and ongoing clinical trials were excluded. Nine studies with 754 participants were identified. A forest plot revealed that the incidence of postoperative neurocognitive dysfunction did not differ between the xenon anesthesia and control groups (P = 0.43). Additionally, xenon anesthesia significantly shortened the emergence time for time to opening eyes (P < 0.001), time to extubation (P < 0.001), time to react on demand (P = 0.01), and time to time and spatial orientation (P = 0.04). However, the Aldrete score significantly increased with xenon anesthesia (P = 0.005). Postoperative complications did not differ between the anesthesia groups. Egger's test for bias showed no small-study effect, and a trim-and-fill analysis showed no apparent publication bias. In conclusion, xenon anesthesia probably did not affect the occurrence of postoperative neurocognitive dysfunction. However, xenon anesthesia may effectively shorten the emergence time of certain parameters without adverse effects.


Assuntos
Anestésicos , Delírio , Adulto , Humanos , Criança , Xenônio/farmacologia , Período Pós-Operatório , Anestesia por Inalação/efeitos adversos , Delírio/induzido quimicamente
8.
Molecules ; 28(22)2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-38005238

RESUMO

Paclitaxel, a natural secondary metabolite isolated and purified from the bark of the Taxus tree, is considered one of the most successful natural anticancer drugs due to its low toxicity, high potency and broad-spectrum anticancer activity. Taxus trees are scarce and slow-growing, and with extremely low paclitaxel content, the contradiction between supply and demand in the market is becoming more and more intense. Therefore, researchers have tried to obtain paclitaxel by various methods such as chemical synthesis, artificial culture, microbial fermentation and tissue cell culture to meet the clinical demand for this drug. This paper provides a comprehensive overview of paclitaxel extraction, combination therapy, total synthesis, semi-synthesis and biosynthesis in recent years and provides an outlook, aiming to provide a theoretical basis and reference for further research on the production and application of paclitaxel in the future.


Assuntos
Paclitaxel , Taxus , Paclitaxel/química , Fermentação , Taxus/química
9.
J Otolaryngol Head Neck Surg ; 52(1): 72, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37932841

RESUMO

BACKGROUND: The management of locally advanced recurrent nasopharyngeal carcinoma (rNPC) is challenging. The objective of our study was to compare salvage endoscopic nasopharyngectomy (ENPG) with intensity-modulated radiotherapy (IMRT) in clinical outcomes and complications of locally advanced rNPC. METHODS: Patients with histologically confirmed rNPC in rT3-4N0-3M0 stages were retrospectively enrolled between January 2013 and December 2019 in this multicenter, case-matched study. The baseline clinicopathological characteristics of patients were balanced by propensity score matching between the ENPG and IMRT groups. ENPG was performed in patients with easily or potentially resectable tumors. The oncological outcomes as well as treatment-related complications were compared between two groups. RESULTS: A total of 176 patients were enrolled and 106 patients were matched. The ENPG group (n = 53) and the IMRT group (n = 53) showed comparable outcomes in the 3-year overall survival rate (68.4% vs. 65.4%, P = 0.401), cancer-specific survival rate (80.9% vs. 74.4%, P = 0.076), locoregional failure-free survival rate (36.6% vs. 45.3%, P = 0.076), and progression-free survival rate (27.5% vs. 32.3%, P = 0.216). The incidence of severe treatment-related complications of patients in the ENPG group was lower than that in the IMRT group (37.7% vs. 67.9%, P = 0.002). The most common complications were post perioperative hemorrhage (13.2%) in ENPG group and temporal lobe necrosis (47.2%) in IMRT group, respectively. CONCLUSION: Salvage ENPG exhibits comparable efficacy but less toxicities than IMRT in carefully screened patients with locally advanced rNPC, which may be a new choice of local treatment.


Assuntos
Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Humanos , Carcinoma Nasofaríngeo , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia
10.
Ear Nose Throat J ; : 1455613231205531, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37970792

RESUMO

Parapharyngeal infection is a well-known disease of otorhinolaryngologists. Rapid onset, short duration, severe symptoms, and manifestations such as sore throat and dysphagia are common characteristics treated primarily by surgical incision and drainage. Traditional surgical approaches encompass endoscopic transoral/nasal, transparotid, transcervical, or a combination thereof. We report a novel technique of nasal endoscopic incision and drainage transnasal retropterygoid approach to an upper parapharyngeal abscess. This report presents a case of a 14-year-old man presented with severe right neck and head pain, who was found to have an upper parapharyngeal abscess during a nasal endoscopic parapharyngeal exploration via a retropterygoid approach. The intraoperative frozen section revealed chronic mucosal inflammation and mild to moderate dysplasia of the squamous epithelium, but no carcinoma.

11.
Mediators Inflamm ; 2023: 1400267, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38022687

RESUMO

Background: 5-Methylcytosine (m5C) RNA modification is closely implicated in the occurrence of a variety of cancers. Here, we established a novel prognostic signature for ovarian cancer (OC) patients based on m5C RNA modification-related genes and explored the correlation between these genes with the tumor immune microenvironment. Methods: Methylated-RNA immunoprecipitation sequencing helped us to identify candidate genes related to m5C RNA modification at first. Based on TCGA database, we screened the differentially expressed candidate genes related to the prognosis and constructed a prognostic model using LASSO Cox regression analyses. Notably, the accuracy of the model was evaluated by Kaplan-Meier analysis and receiver operator characteristic curves. Independent prognostic risk factors were investigated by Cox proportional hazard model. Furthermore, we also analyzed the biological functions and pathways involved in the signature. Finally, the immune response of the model was visualized in great detail. Results: Totally, 2,493 candidate genes proved to be involved in m5C modification of RNA for OC. We developed a signature with prognostic value consisting of six m5C RNA modification-related genes. Specially, samples have been split into two cohorts with low- and high-risk scores according to the model, in which the low-risk OC patients exhibited dramatically better overall survival time than those with high-risk scores. Besides, not only was this model a prognostic factor independent of other clinical characteristics but it predicted the intensity of the immune response in OC. Significantly, the accuracy and availability of the signature were verified by ICGC database. Conclusions: Our study bridged the gap between m5C RNA modification and the prognosis of OC and was expected to provide an effective breakthrough for immunotherapy in OC patients.


Assuntos
Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/terapia , Prognóstico , Bases de Dados Factuais , Imunoterapia , RNA , Microambiente Tumoral/genética
12.
Biomater Sci ; 11(21): 7077-7089, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37655798

RESUMO

Tissue engineering techniques bring the promise of vaginal reconstruction with low invasiveness and fewer complications. However, existing biomaterial scaffolds remain limited in efficient vaginal recovery, focusing only on regenerating an epithelial layer, but muscle layers are missing or abnormal. The lack of a multi-tissue hierarchical structure in the reconstructed vagina leads to shrinking, stenosis, and fibrosis. Here, an acellular matrix named a double-sided biomembrane (DBM) is demonstrated for vaginal recovery. The regeneration of epithelial and muscle layers is achieved simultaneously since the smooth side of the DBM is helpful for guiding epithelial cell growth, while its loose and porous side guides muscle cell growth. In addition, the DBM demonstrates excellent mechanical properties similar to vaginal tissue, and hydrophilicity. Therefore, neovaginas were observed in the fourth and twelfth weeks after DBMs were transplanted to repair full-thickness vaginal defects (4 cm) that we established in large animals. The DBMs can effectively promote rapid epithelialization, the formation of large muscle bundles, higher rates of angiogenesis, and the restoration of physiological function in a neovagina. That is, the injured vagina achieves nearly complete recovery in anatomy and function, similar to a normal vagina. These preclinical results indicate that the DBM has prospects for vaginal injury repair.

13.
Int J Mol Med ; 52(4)2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37615174

RESUMO

Prolonging the reproductive lifespan is beneficial for preserving the physical and psychological health of women. The transplantation of mesenchymal stem cell (MSC)­derived exosomes (MSC­Exos) has been reported to be a promising regenerative therapeutic strategy for restoring the function of aging ovaries. The present study thus evaluated the therapeutic efficacy of exosomes derived from human umbilical cord­MSCs (hUCMSC­Exos) in a mouse model of natural ovarian aging (NOA), and further investigated the role of exosomal microRNAs (miRNAs/miRs) in the mechanisms of this creative therapy. Specifically, following the administration of hUCMSC­Exos in mice with NOA, ovarian function was found to improve, as indicated by the restoration of follicle numbers and hormone levels. These exosomes were found to exhibit the ability to inhibit PTEN expression and suppress apoptosis both in vivo and in vitro. Subsequently, miRNA sequencing of the exosomes was performed, following which bioinformatics analysis was used to identify the highly expressed miRNAs that are capable of targeting PTEN expression. Through high­throughput sequencing and molecular analyses, miR­21­5p was found to be the highest in ranking in terms of expression, suggesting that hUCMSC­Exos can preserve ovarian function by suppressing PTEN expression to inhibit apoptosis by delivering miR­21­5p. On the whole, the results of the present study suggest that the application of exosomes can be used to restore ovarian function in mice with NOA. These positive findings also suggest that the transplantation of exosomes derived from MSCs holds promise as an agent against ovarian aging.


Assuntos
Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Humanos , Feminino , Animais , Camundongos , MicroRNAs/genética , Envelhecimento , Apoptose , Fatores Imunológicos
14.
Nat Commun ; 14(1): 4509, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37495568

RESUMO

Oxidation of renewable polyol/sugar into formic acid using molecular O2 over heterogeneous catalysts is still challenging due to the insufficient activation of both O2 and organic substrates on coordination-saturated metal oxides. In this study, we develop a defective MnO2 catalyst through a coordination number reduction strategy to enhance the aerobic oxidation of various polyols/sugars to formic acid. Compared to common MnO2, the tri-coordinated Mn in the defective MnO2 catalyst displays the electronic reconstruction of surface oxygen charge state and rich surface oxygen vacancies. These oxygen vacancies create more Mnδ+ Lewis acid site together with nearby oxygen as Lewis base sites. This combined structure behaves much like Frustrated Lewis pairs, serving to facilitate the activation of O2, as well as C-C and C-H bonds. As a result, the defective MnO2 catalyst shows high catalytic activity (turnover frequency: 113.5 h-1) and formic acid yield (>80%) comparable to noble metal catalysts for glycerol oxidation. The catalytic system is further extended to the oxidation of other polyols/sugars to formic acid with excellent catalytic performance.

15.
Medicine (Baltimore) ; 102(29): e34385, 2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37478247

RESUMO

BACKGROUND: Postoperative nausea and vomiting (PONV) is one of the common adverse reactions after surgery. Recent randomized controlled trials (RCTs) investigating antiemetic drugs suggest that aprepitant has the strongest antiemetic effect of any single drug. This meta-analysis aimed to explore the efficacy of aprepitant for preventing PONV based on the existing literature. METHODS: To identify RCTs investigating the use of aprepitant for PONV prevention, we searched PubMed, Embase, and Cochrane Library databases for articles published prior to March 20, 2022. Seventeen RCTs were identified, with 3299 patients, meeting the inclusion criteria. PONV incidence, complete response, 80 mg aprepitant combined with dexamethasone and ondansetron, vomiting, nausea, and analgesic dose-response were the main outcomes measured. RESULTS: Compared with the control group, PONV incidence was significantly reduced among those receiving aprepitant (odds ratio [OR]: 0.34; 95% confidence interval [CI]: 0.26, 0.44; P < .0001), with a more complete response (OR: 1.35; 95% CI: 1.14, 1.59; P = .0004). Supplementation of 80 mg aprepitant in combination with dexamethasone and ondansetron substantially improved the effects of PONV (OR: 0.36; 95% CI: 0.16, 0.82; P = .01). Further, administration of 80 mg aprepitant was better at preventing vomiting than nausea (OR: 8.6; 95% CI: 3.84, 19. 29; P < .00001). No statistically significant difference between the dose-response of analgesics was identified (mean difference: -1.09; 95% CI: -6.48, 4.30; P = .69). The risk of bias was assessed independently by paired evaluators. CONCLUSION: Aprepitant effectively reduces the incidence of PONV; however, the effects of postoperative analgesia require further exploration.


Assuntos
Antieméticos , Náusea e Vômito Pós-Operatórios , Humanos , Aprepitanto , Náusea e Vômito Pós-Operatórios/prevenção & controle , Náusea e Vômito Pós-Operatórios/tratamento farmacológico , Ondansetron/uso terapêutico , Morfolinas/uso terapêutico , Antieméticos/uso terapêutico , Vômito/tratamento farmacológico , Dexametasona/uso terapêutico
16.
J Control Release ; 358: 654-666, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37209961

RESUMO

As most solid tumors are characterized by a hypoxic microenvironment, enormous efforts have been made to develop strategies to fight hypoxia. This study shows that ivermectin (IVM), an antiparasitic drug, is able to alleviate tumor hypoxia by inhibiting mitochondrial respiration. We explore this to strengthen oxygen-dependent photodynamic therapy (PDT) using chlorin e6 (Ce6) as a photosensitizer. To synergize their pharmacological behaviors, Ce6 and IVM are encapsulated into stable Pluronic F127 micelles. The micelles are uniform in size and seem well-suited for the co-delivery of Ce6 and IVM. The micelles could passively target the drugs into tumors and enhance their cellular internalization. Most importantly, through mitochondrial dysfunction, the micelles reduce the oxygen consumption (making the tumor less hypoxic). Consequently, the production of reactive oxygen species would be increase which, in turn, improves the efficacy of PDT against hypoxic tumors.


Assuntos
Fotoquimioterapia , Porfirinas , Humanos , Micelas , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/uso terapêutico , Hipóxia/tratamento farmacológico , Mitocôndrias , Porfirinas/uso terapêutico
17.
J Am Chem Soc ; 145(13): 7095-7100, 2023 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-36961225

RESUMO

Selective, efficient, and controllable oxidation of cytosine modifications is valuable for epigenetic analyses, yet only limited progress has been made. Here, we present two modular chemical oxidation reactions: conversion of 5-hydroxymethylcytosine (5hmC) into 5-formylcytosine (5fC) using 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (ACT+BF4-) and further transformation of 5fC into 5-carboxycytosine (5caC) through Pinnick oxidation. Both reactions are mild and efficient on double-stranded DNA. We integrated these two oxidations with borane reduction to develop chemical-assisted pyridine borane sequencing plus (CAPS+), for direct and quantitative mapping of 5hmC. Compared with CAPS, CAPS+ improved the conversion rate and false-positive rate. We applied CAPS+ to mouse embryonic stem cells, human normal brain, and glioblastoma DNA samples and demonstrated its superior sensitivity in analyzing the hydroxymethylome.


Assuntos
Cistina , Cistina/análise , Humanos , Animais , Camundongos , Metilação de DNA , DNA/genética , Oxirredução
18.
Int J Mol Sci ; 24(3)2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36768267

RESUMO

The transcription factor SOX11 is a tumor-associated antigen with low expression in normal cells, but overexpression in glioblastoma (GBM). So far, conventional surgery, chemotherapy, and radiotherapy have not substantially improved the dismal prognosis of relapsed/refractory GBM patients. Immunotherapy is considered a promising strategy against GBM, but there is a fervent need for better immunotargets in GBM. To this end, we performed an in silico prediction study on SOX11, which primarily yielded ten promising HLA-A*0201-restricted peptides derived from SOX11. We defined a novel peptide FMACSPVAL, which had the highest score according to in silico prediction (6.02 nM by NetMHC-4.0) and showed an exquisite binding affinity to the HLA-A*0201 molecule in the peptide-binding assays. In the IFN-γ ELISPOT assays, FMACSPVAL demonstrated a high efficiency for generating SOX11-specific CD8+ T cells. Nine out of thirty-two healthy donors showed a positive response to SOX11, as assessed by the ELISPOT assays. Therefore, this novel antigen peptide epitope seems to be promising as a target for T cell-based immunotherapy in GBM. The adoptive transfer of in vitro elicited SOX11-specific CD8+ T cells constitutes a potential approach for the treatment of GBM patients.


Assuntos
Glioblastoma , Glioma , Humanos , Linfócitos T CD8-Positivos , Epitopos de Linfócito T , Glioma/metabolismo , Glioblastoma/metabolismo , Peptídeos/química , Imunoterapia , Linfócitos T Citotóxicos , Fatores de Transcrição SOXC/metabolismo
19.
Mini Rev Med Chem ; 23(18): 1780-1796, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36825714

RESUMO

Paclitaxel is an anticancer drug first isolated from the bark of the Pacific yew tree. It has been widely used for the treatment of ovarian, breast, uterine and other cancers because of its low toxicity, high efficiency and broad-spectrum anticancer activity, and it is considered to be one of the most successful natural anticancer drugs available. Paclitaxel is a microtubule-targeting drug whose main molecular mechanism is to disrupt microtubule dynamics and induce mitotic arrest and cell death. Despite the many clinical successes of paclitaxel, the extraction of natural paclitaxel from Taxus species has proven to be environmentally unsustainable and economically unviable. As a result, researchers are constantly working to find innovative ways to meet society's need for this drug. Currently, many methods, including artificial cultivation, microbial fermentation, chemical synthesis, and tissue and cell culture, have been explored and developed to obtain paclitaxel. In addition, the poor water solubility of paclitaxel has led to significant limitations in its clinical application. Conventional paclitaxel formulations use Cremophor EL and ethanol to dissolve paclitaxel, which can lead to serious side effects. In recent decades, a series of new nanotechnology-based paclitaxel dosage forms have been developed, including albumin-bound paclitaxel, polymeric micellar paclitaxel, polymer-paclitaxel couples, and liposome-encapsulated paclitaxel. These nanoformulations can significantly reduce the toxicity of paclitaxel and greatly improve its anti-tumor efficiency. This paper reviews the development of the production, dosage form and combination therapy of paclitaxel in recent years and presents an outlook, with the aim of providing a theoretical basis and reference for further research on the production and application of paclitaxel in the future.


Assuntos
Antineoplásicos Fitogênicos , Antineoplásicos , Neoplasias , Humanos , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Polímeros/química
20.
Pain Ther ; 12(1): 117-139, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36227420

RESUMO

INTRODUCTION: Determining the prevalence of chronic postsurgical pain (CPSP) after video-assisted thoracoscopic surgery (VATS) and identifying CPSP predictors should improve the prognosis of patients undergoing VATS. Although several studies have investigated predictors of CPSP after VATS, there were significant dissimilarities in the findings due to the confounding of predictors. METHODS: PubMed, Cochrane, MEDLINE, Web of Science, Chinese Biomedical Literature, and China National Knowledge Infrastructure databases were comprehensively searched using the Medical Subject Headings terms "pain, postoperative," "thoracic surgery, video-assisted," and all related free terms from inception until March 27, 2022. The Stata metaprop package was used to comprehensively analyze the incidence of CPSP following VATS. Furthermore, the pooled odds ratios (OR) or the standardized mean differences (SMD) and their corresponding 95% confidence intervals (95% CI) were calculated, and qualitative analyses were performed for predictors that could not be assessed quantitatively to evaluate the effects of the included risk factors on the occurrence of CPSP. Unadjusted odds ratios were utilized to consider the impact of non-significant estimates if the original study did not report them. RESULTS: Of the 4302 studies, 183 were considered eligible, and 17 were finally included in this study. The overall incidence of CPSP after VATS was 35.3% (95% CI 27.1-43.5%). The qualitative synthesis results revealed that female sex, age, and acute postoperative pain were definite predictors of CPSP after VATS. The number of ports, operation time, duration of drainage, and insufficient analgesia were also considered predictors. Consistent, quantitative synthesis results also showed that the aforementioned predictors were closely related to the occurrence of CPSP after VATS. Only by quantitative analysis, postoperative chemotherapy and an educational level less than junior school were also risk factors for CPSP. Other predictors displayed no evidence or unclear evidence of association with CPSP after VATS. CONCLUSION: This study preliminarily determined the incidence of CPSP after VATS based on the existing literature. Female sex, age, and acute pain were identified as risk factors for CPSP after VATS, and other potential risk factors were also identified and analyzed. However, as a result of the inclusion of retrospective studies and inevitable limitations in this systematic review and meta-analysis, the results of this study still need to be verified by large-scale prospective clinical studies. TRIAL REGISTRATION: CRD42022323179.

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