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1.
Front Bioeng Biotechnol ; 12: 1396892, 2024.
Article En | MEDLINE | ID: mdl-38720877

Hydrogel is considered as a promising candidate for wound dressing due to its tissue-like flexibility, good mechanical properties and biocompatibility. However, traditional hydrogel dressings often fail to fulfill satisfied mechanical, antibacterial, and biocompatibility properties simultaneously, due to the insufficient intrinsic bactericidal efficacy and the addition of external antimicrobial agents. In this paper, hydroxyl-contained acrylamide monomers, N-Methylolacrylamide (NMA) and N-[Tris (hydroxymethyl)methyl] acrylamide (THMA), are employed to prepare a series of polyacrylamide hydrogel dressings xNMA-yTHMA, where x and y represent the mass fractions of NMA and THMA in the hydrogels. We have elucidated that the abundance of hydroxyl groups determines the antibacterial effect of the hydrogels. Particularly, hydrogel 35NMA-5THMA exhibits excellent mechanical properties, with high tensile strength of 259 kPa and large tensile strain of 1737%. Furthermore, the hydrogel dressing 35NMA-5THMA demonstrates remarkable inherent antibacterial without exogenous antimicrobial agents owing to the existence of abundant hydroxyl groups. Besides, hydrogel dressing 35NMA-5THMA possesses excellent biocompatibility, in view of marginal cytotoxicity, low hemolysis ratio, and negligible inflammatory response and organ toxicity to mice during treatment. Encouragingly, hydrogel 35NMA-5THMA drastically promote the healing of bacteria-infected wound in mice. This study has revealed the importance of polyhydroxyl in the antibacterial efficiency of hydrogels and provided a simplified strategy to design wound healing dressings with translational potential.

2.
Small ; : e2309891, 2024 May 09.
Article En | MEDLINE | ID: mdl-38721972

Although the current cancer photothermal therapy (PTT) can produce a powerful therapeutic effect, tumor cells have been proved a protective mechanism through autophagy. In this study, a novel hybrid theranostic nanoparticle (CaCO3@CQ@pDB NPs, CCD NPs) is designed and prepared by integrating a second near-infrared (NIR-II) absorbed conjugated polymer DTP-BBT (pDB), CaCO3, and autophagy inhibitor (chloroquine, CQ) into one nanosystem. The conjugated polymer pDB with asymmetric donor-acceptor structure shows strong NIR-II absorbing capacity, of which the optical properties and photothermal generation mechanism of pDB are systematically analyzed via molecular theoretical calculation. Under NIR-II laser irradiation, pDB-mediated PTT can produce powerful killing ability to tumor cells. At the same time, heat stimulates a large amount of Ca2+ inflow, causing calcium overload induced mitochondrial damage and enhancing the apoptosis of tumor cells. Besides, the released CQ blocks the self-protection mechanism of tumor cells and greatly enhances the attack of PTT and calcium overload therapy. Both in vitro and in vivo experiments confirm that CCD NPs possess excellent NIR-II theranostic capacity, which provides a new nanoplatform for anti-tumor therapy and builds great potential for future clinical research.

3.
ACS Chem Biol ; 2024 May 09.
Article En | MEDLINE | ID: mdl-38723147

As an important functional monosaccharide, glucosamine (GlcN) is widely used in fields such as medicine, food nutrition, and health care. Here, we report a distinct GlcN biosynthesis method that utilizes engineered Bacillus subtilis glucosamine-6-phosphate synthase (BsGlmS) to convert D-fructose to directly generate GlcN. The best variant obtained by using a combinatorial active-site saturation test/iterative saturation mutagenesis (CAST/ISM) strategy was a quadruple mutant S596D/V597G/S347H/G299Q (BsGlmS-BK19), which has a catalytic activity 1736-fold that of the wild type toward D-fructose. Upon using mutant BK19 as a whole-cell catalyst, D-fructose was converted into GlcN with 65.32% conversion in 6 h, whereas the wild type only attained a conversion rate of 0.31% under the same conditions. Molecular docking and molecular dynamics simulations were implemented to provide insights into the mechanism underlying the enhanced activity of BK19. Importantly, the BsGlmS-BK19 variant specifically catalyzes D-fructose without the need for phosphorylated substrates, representing a significant advancement in GlcN biosynthesis.

4.
Front Public Health ; 12: 1329768, 2024.
Article En | MEDLINE | ID: mdl-38737867

Objectives: This study aimed to analyze the influencing factors of hospitalization cost of hypertensive patients in TCM (traditional Chinese medicine, TCM) hospitals, which can provide a scientific basis for hospitals to control the hospitalization cost of hypertension. Methods: In this study, 3,595 hospitalized patients with a primary diagnosis of tertiary hypertension in Tianshui City Hospital of TCM, Gansu Province, China, from January 2017 to June 2022, were used as research subjects. Using univariate analysis to identify the relevant variables of hospitalization cost, followed by incorporating the statistically significant variables of univariate analysis as independent variables in multiple linear regression analysis, and establishing the path model based on the results of the multiple linear regression finally, to explore the factors influencing hospitalization cost comprehensively. Results: The results showed that hospitalization cost of hypertension patients were mainly influenced by length of stay, age, admission pathways, payment methods of medical insurance, and visit times, with length of stay being the most critical factor. Conclusion: The Chinese government should actively exert the characteristics and advantages of TCM in the treatment of chronic diseases such as hypertension, consistently optimize the treatment plans of TCM, effectively reduce the length of stay and steadily improve the health literacy level of patients, to alleviate the illnesses pain and reduce the economic burden of patients.


Hospitalization , Hypertension , Medicine, Chinese Traditional , Humans , Female , Hypertension/economics , Male , Middle Aged , Medicine, Chinese Traditional/economics , Medicine, Chinese Traditional/statistics & numerical data , Hospitalization/economics , Hospitalization/statistics & numerical data , China , Aged , Length of Stay/statistics & numerical data , Length of Stay/economics , Adult , Hospital Costs/statistics & numerical data
5.
Comput Biol Med ; 175: 108495, 2024 Jun.
Article En | MEDLINE | ID: mdl-38697003

Allergic rhinitis is a common allergic disease with a complex pathogenesis and many unresolved issues. Studies have shown that the incidence of allergic rhinitis is closely related to genetic factors, and research on the related genes could help further understand its pathogenesis and develop new treatment methods. In this study, 446 allergic rhinitis-related genes were obtained on the basis of the DisGeNET database. The protein-protein interaction network was searched using the random-walk-with-restart algorithm with these 446 genes as seed nodes to assess the linkages between other genes and allergic rhinitis. Then, this result was further examined by three screening tests, including permutation, interaction, and enrichment tests, which aimed to pick up genes that have strong and special associations with allergic rhinitis. 52 novel genes were finally obtained. The functional enrichment test confirmed their relationships to the biological processes and pathways related to allergic rhinitis. Furthermore, some genes were extensively analyzed to uncover their special or latent associations to allergic rhinitis, including IRAK2 and MAPK, which are involved in the pathogenesis of allergic rhinitis and the inhibition of allergic inflammation via the p38-MAPK pathway, respectively. The new found genes may help the following investigations for understanding the underlying molecular mechanisms of allergic rhinitis and developing effective treatments.


Protein Interaction Maps , Rhinitis, Allergic , Humans , Rhinitis, Allergic/genetics , Protein Interaction Maps/genetics , Databases, Genetic , Algorithms , Computational Biology/methods , Gene Regulatory Networks
6.
Sci Rep ; 14(1): 11485, 2024 05 20.
Article En | MEDLINE | ID: mdl-38769391

This study intends to use the basic information and blood routine of schistosomiasis patients to establish a machine learning model for predicting liver fibrosis. We collected medical records of Schistosoma japonicum patients admitted to a hospital in China from June 2019 to June 2022. The method was to screen out the key variables and six different machine learning algorithms were used to establish prediction models. Finally, the optimal model was compared based on AUC, specificity, sensitivity and other indicators for further modeling. The interpretation of the model was shown by using the SHAP package. A total of 1049 patients' medical records were collected, and 10 key variables were screened for modeling using lasso method, including red cell distribution width-standard deviation (RDW-SD), Mean corpuscular hemoglobin concentration (MCHC), Mean corpuscular volume (MCV), hematocrit (HCT), Red blood cells, Eosinophils, Monocytes, Lymphocytes, Neutrophils, Age. Among the 6 different machine learning algorithms, LightGBM performed the best, and its AUCs in the training set and validation set were 1 and 0.818, respectively. This study established a machine learning model for predicting liver fibrosis in patients with Schistosoma japonicum. The model could help improve the early diagnosis and provide early intervention for schistosomiasis patients with liver fibrosis.


Liver Cirrhosis , Machine Learning , Schistosoma japonicum , Schistosomiasis japonica , Humans , Liver Cirrhosis/blood , Liver Cirrhosis/diagnosis , Liver Cirrhosis/parasitology , Liver Cirrhosis/pathology , Schistosomiasis japonica/diagnosis , Schistosomiasis japonica/blood , Male , Female , Middle Aged , Adult , Animals , China , Erythrocyte Indices , Algorithms , Aged
7.
Drug Des Devel Ther ; 18: 1613-1625, 2024.
Article En | MEDLINE | ID: mdl-38774484

Purpose: Remimazolam, an ultra-short-acting and fast-metabolized sedative, has only been sporadically investigated in children. This study was performed to determine the beneficial effects of intranasal remimazolam or dexmedetomidine on preoperative anxiety in children undergoing general surgeries. Patients and Methods: Ninety children were randomly and equally assigned to Group R (intranasal remimazolam 1.5mg kg-1), Group D (intranasal dexmedetomidine 2 mcg kg-1), and Group C (intranasal distilled water). The primary outcomes were the preoperative anxiety scores using the modified Yale preoperative anxiety scale (m-Ypas). The secondary outcomes included the cooperation behaviour of intranasal drug application, preoperative sedation levels, parental separation anxiety scores (PSAS), and mask acceptance scores (MAS). Results: Group R showed a significant low anxiety at 10 min after intranasal premedication (vs group C, P=0.010; vs group D, P = 0.002) and at anaesthesia induction (vs group C, P = 0.004). Group D showed a significantly low anxiety score only prior to anaesthesia induction (vs group C, P = 0.005). Most children in group R achieved mild sedation at 10 min (vs group C, P < 0.001; vs group D, P < 0.001), with a few progressing to deep sedation afterwards, while group D tended toward deep sedation. Compared to Group C, patients in Group R performed significantly better on the MAS (P = 0.014) and PSAS (P = 0.008). However, remimazolam did cause poor cooperation behavior to the intranasal application due to its mucosal irritation (vs group C, P = 0.001; vs group D, P = 0.010). Conclusion: Both intranasal remimazolam and dexmedetomidine can effectively alleviate preoperative anxiety in children. While intranasal remimazolam has a rapid onset, it produces only mild sedation and causes substantial nasal irritation. Trial Registration: NCT04720963, January 22, 2021, ClinicalTrials.Gov.


Administration, Intranasal , Anti-Anxiety Agents , Anxiety , Dexmedetomidine , Hypnotics and Sedatives , Humans , Dexmedetomidine/administration & dosage , Dexmedetomidine/pharmacology , Hypnotics and Sedatives/administration & dosage , Hypnotics and Sedatives/pharmacology , Male , Female , Anti-Anxiety Agents/administration & dosage , Anti-Anxiety Agents/pharmacology , Child , Child, Preschool , Anxiety/drug therapy , Benzodiazepines/administration & dosage , Benzodiazepines/pharmacology , Double-Blind Method
8.
Anesthesiology ; 2024 May 16.
Article En | MEDLINE | ID: mdl-38758221

BACKGROUND: Preventing emergence delirium is a clinical goal for pediatric anesthesia, yet there is no consensus on its prevention. This study investigated the hypothesis that a continuous infusion or a single bolus of remimazolam can reduce the incidence of emergence delirium in children. METHODS: A hundred and twenty children aged 1-6 years old were randomly and equally allocated into three groups: group RC, which received a continuous infusion of remimazolam at 1 mg kg -1 h -1; group RB, which received a single bolus of remimazolam at 0.2 mg kg -1 at the beginning of wound closure; and group C, which received a continuous infusion of saline at 1 mL kg -1 h -1 and single bolus of saline at 0.2 mL kg -1 at the beginning of sutures. The primary outcome was the incidence of emergence delirium assessed by pediatric anesthesia emergence delirium (PAED) scale. Secondary outcomes included the number of rescues propofol administrations in the post-anesthesia care unit (PACU), recovery time, end-tidal sevoflurane concentration when maintaining BIS within the range of 40-60, and adverse events. RESULTS: The incidence of emergence delirium in group RC (5%, vs. group C, risk ratio, 0.14; 95% CI, 0.04 to 0.59; P=0.001) and group RB (7.7%, vs. group C, risk ratio, 0.22; 95% CI, 0.07 to 0.71; P=0.003) was significantly lower compared with group C (32.5%). Propofol was given to 2 patients in each of groups RC and RB to treat delirium and to 10 patients in group C (group RC vs. group C, risk ratio, 0.20; 95% CI, 0.05 to 0.86; P=0.012; group RB vs. group C, risk ratio, 0.21; 95% CI, 0.05 to 0.88; P=0.014). No differences in the recovery time and adverse effects were detected. CONCLUSIONS: Both continuous infusion and single bolus administration of remimazolam can effectively reduce the occurrence of emergence delirium in children.

9.
J Craniofac Surg ; 2024 May 17.
Article En | MEDLINE | ID: mdl-38758539

Hemimasticatory spasm (HMS) combined with hemifacial atrophy is a rare clinical entity with an unclear etiology. The authors report a 58-year-old female suffering from HMS and hemifacial atrophy, which performed microvascular decompression plus partial resection of the trigeminal nerve motor root, which is the first report in worldwide. The vascular compression of the trigeminal nerve motor root was found in surgery, the authors completed the aforementioned surgical method. The symptoms of HMS disappeared after surgery but recurred after 8 months.

10.
Pediatr Res ; 2024 May 06.
Article En | MEDLINE | ID: mdl-38710942

BACKGROUND: This study aims to investigate the role of endoplasmic reticulum stress (ER stress) in human dermal lymphatic endothelial cells (HDLECs) and lymphatic malformations (LMs) and its relationship with aerobic glycolysis and inflammation. METHODS: The proliferation and apoptosis of HDLECs were examined with lipopolysaccharide (LPS) treatment. ER stress-associated proteins and glycolysis-related markers were detected by western blot. Glycolysis indexes were detected by seahorse analysis and lactic acid production assay kits. Immunohistochemistry was used to reveal the ER stress state of lymphatic endothelial cells (LECs) in LMs. RESULTS: LPS induced ER stress in HDLECs but did not trigger detectable apoptosis. Intriguingly, LPS-treated HDLECs also showed increased glycolysis flux. Knockdown of Hexokinase 2, a key enzyme for aerobic glycolysis, significantly inhibited the ability of HDLECs to resist ER stress-induced apoptosis. Moreover, compared to normal skin, glucose-regulated protein 78 (GRP78/BIP), and phosphorylation protein kinase R-like kinase (p-PERK), two key ER stress-associated markers, were upregulated in LECs of LMs, which was correlated with the inflected state. In addition, excessively activated ER stress inhibited the progression of LMs in rat models. CONCLUSIONS: These data indicate that glycolysis could rescue activated ER stress in HDLECs, which is required for the accelerated development of LMs. IMPACT: Inflammation enhances both ER stress and glycolysis in LECs while glycolysis is required to attenuate the pro-apoptotic effect of ER stress. Endoplasmic reticulum (ER) stress is activated in lymphatic endothelial cells (LECs) of LMs, especially in inflammatory condition. The expression of ER stress-related proteins is increased in LMs and correlated with Hexokinase 2 expression. Pharmacological activation of ER stress suppresses the formation of LM lesions in the rat model. ER stress may be a promising and effective therapeutic target for the treatment of LMs.

11.
Med Image Anal ; 95: 103204, 2024 May 15.
Article En | MEDLINE | ID: mdl-38761438

Due to the intra-class diversity of mitotic cells and the morphological overlap with similarly looking imposters, automatic mitosis detection in histopathology slides is still a challenging task. In this paper, we propose a novel mitosis detection model in a weakly supervised way, which consists of a candidate proposal network and a verification network. The candidate proposal network based on patch learning aims to separate both mitotic cells and their mimics from the background as candidate objects, which substantially reduces missed detections in the screening process of candidates. These obtained candidate results are then fed into the verification network for mitosis refinement. The verification network adopts an RBF-based subcategorization scheme to deal with the problems of high intra-class variability of mitosis and the mimics with similar appearance. We utilize the RBF centers to define subcategories containing mitotic cells with similar properties and capture representative RBF center locations through joint training of classification and clustering. Due to the lower intra-class variation within a subcategory, the localized feature space at subcategory level can better characterize a certain type of mitotic figures and can provide a better similarity measurement for distinguishing mitotic cells from nonmitotic cells. Our experiments manifest that this subcategorization scheme helps improve the performance of mitosis detection and achieves state-of-the-art results on the publicly available mitosis datasets using only weak labels.

12.
ACS Med Chem Lett ; 15(5): 595-601, 2024 May 09.
Article En | MEDLINE | ID: mdl-38746892

Herein we describe the medicinal chemistry efforts that led to the discovery of the clinical-staged Syk inhibitor sovleplenib (41) via a structure-activity relationship investigation and pharmacokinetics (PK) optimization of a pyrido[3,4-b]pyrazine scaffold. Sovleplenib is a potent and selective Syk inhibitor with favorable preclinical PK profiles and robust anti-inflammation efficacy in a preclinical collagen-induced arthritis model. Sovleplenib is now being developed for treating autoimmune diseases such as immune thrombocytopenic purpura and warm antibody hemolytic anemia as well as hematological malignancies.

13.
Mater Horiz ; 2024 Apr 03.
Article En | MEDLINE | ID: mdl-38567484

Discovering new negative thermal expansion (NTE) materials is a great challenge in experiment. Meanwhile, the machine learning (ML) method can be another approach to explore NTE materials using the existing material databases. Herein, we adopt the multi-step ML method with efficient data augmentation and cross-validation to identify around 1000 materials, including oxides, fluorides, and cyanides, with bulk framework structures as new potential NTE candidate materials from ICSD and other databases. Their corresponding coefficients of negative thermal expansion (CNTE) and temperature ranges are also well predicted. Among them, about 57 materials are predicted to have an NTE probability of 100%. Some predicted NTE materials were tested by the first-principles calculations with quasi-harmonic approximation (QHA), which indicates that the ML results are in good agreement with the first principles calculation results. Based on the comprehensive analysis of the existing and predicted NTE materials, we established three universal relationships of CNTE with an average electronegativity, porosity, and temperature range. From these, we also identified some important critical values characterizing the NTE property, which can serve as an important criterion for designing new NTE materials.

14.
Small ; : e2400919, 2024 Apr 19.
Article En | MEDLINE | ID: mdl-38639010

Triple-negative breast cancer (TNBC) is a highly aggressive and uncommon subtype of breast cancer with a poor prognosis. It is crucial to prioritise the creation of a nanotherapeutic method that is highly selective and actively targeting TNBC. This study explores a new nanosystem, Cu9S8-SNAP@PM (C-S@P), composed of Cu9S8-SNAP coated with a platelet membrane (PM). The purpose of this nanosystem is to cure TNBC using multimodal therapy. The utilisation of PM-coated nanoparticles (NPs) enables active targeting, leading to the efficient accumulation of C-S@P within the tumour. The Cu9S8 component within these NPs serves the potential to exert photothermal therapy (PTT) and chemodynamic therapy (CDT). Simultaneously, the S-Nitroso-N-Acetylvanicillamine (SNAP) component enables nitric oxide (NO) gas therapy (GT). Furthermore, when exposed to NIR-II laser light, Cu9S8 not only increases the temperature of the tumour area for PTT, but also boosts CDT and stimulates the release of NO through thermal reactions to improve the effectiveness of GT. Both in vitro and in vivo experimental results validate that C-S@P exhibits minimal side effects and represents a multifunctional nano-drug targeted at tumors for efficient treatment. This approach promises significant potential for TNBC therapy and broader applications in oncology.

15.
Proteomics ; : e2300371, 2024 Apr 21.
Article En | MEDLINE | ID: mdl-38643379

Forecasting alterations in protein stability caused by variations holds immense importance. Improving the thermal stability of proteins is important for biomedical and industrial applications. This review discusses the latest methods for predicting the effects of mutations on protein stability, databases containing protein mutations and thermodynamic parameters, and experimental techniques for efficiently assessing protein stability in high-throughput settings. Various publicly available databases for protein stability prediction are introduced. Furthermore, state-of-the-art computational approaches for anticipating protein stability changes due to variants are reviewed. Each method's types of features, base algorithm, and prediction results are also detailed. Additionally, some experimental approaches for verifying the prediction results of computational methods are introduced. Finally, the review summarizes the progress and challenges of protein stability prediction and discusses potential models for future research directions.

16.
Ying Yong Sheng Tai Xue Bao ; 35(3): 648-658, 2024 Mar 18.
Article En | MEDLINE | ID: mdl-38646752

Carbon wet deposition and river carbon output in river basins are important components of global carbon cycle. The assessment of both properties is of great significance for regional carbon budget. However, research on these topics in high-latitude permafrost regions in China is still lacking. We conducted dynamic monitoring of carbon wet deposition and carbon output in the river from May 28th to October 30th, 2022, in Laoyeling watershed, a typical forested watershed in the Da Xing'an Mountains permafrost region. We analyzed the variations of carbon component concentrations and fluxes in precipitation and river water, and estimated the contribution of carbon wet deposition to carbon output in the watershed. The results showed that wet deposition fluxes of dissolved organic carbon (DOC), dissolved inorganic carbon (DIC), and total dissolved carbon (TDC) in the Laoyeling watershed were 1354.86, 684.59, and 2039.45 kg·km-2, respectively. The fluxes of DOC, DIC, TDC, particulate organic carbon (POC), particulate inorganic carbon (PIC), and total carbon (TC) in the river were 601.75, 1977.30, 2579.05, 125.13, 21.99, and 2726.17 kg·km-2, respectively. The contribution of TDC wet deposition to the river TDC output was 9941.89 kg, accounting for 17.6% of total output. The DIC concentration in the river showed significant seasonal differences, with increased runoff resulting from precipitation leading to a decrease in DIC concentration in the river and showing a clear dilution effect, while the concentrations of DOC, POC, and PIC increased, mainly due to erosion effect. In conclusion, carbon wet deposition flux in the Laoyeling watershed was mainly determined by precipitation, and its contribution to river carbon output was relatively small compared to other factor. Runoff was the dominant factor affecting river carbon output. The results would provide important insights into carbon cycling and carbon budget balance in permafrost regions under climate change.


Carbon , Environmental Monitoring , Forests , Permafrost , Rivers , China , Rivers/chemistry , Carbon/analysis , Carbon Cycle , Rain/chemistry , Ecosystem
17.
Sci Rep ; 14(1): 8389, 2024 04 10.
Article En | MEDLINE | ID: mdl-38600093

Pancreatic ductal adenocarcinoma (PDAC) is not sensitive to most chemotherapy drugs, leading to poor chemotherapy efficacy. Recently, Trametinib and Palbociclib have promising prospects in the treatment of pancreatic cancer. This article aims to explore the effects of Trametinib on pancreatic cancer and address the underlying mechanism of resistance as well as its reversal strategies. The GDSC (Genomics of Drug Sensitivity in Cancer) and CTD2 (Cancer Target Discovery and Development) were utilized to screen the potential drug candidate in PDAC cell lines. The dose-increase method combined with the high-dose shock method was applied to induce the Trametinib-resistant PANC-1 and MIA PaCa-2 cell lines. The CCK8 proliferation assay, colony formation assay, flow cytometry, and western blot were conducted to verify the inhibitory effect of Trametinib and Palbociclib. RNA-seq was performed in resistant PDAC cell lines to find the differential expression genes related to drug resistance and predict pathways leading to the reversal of Trametinib resistance. The GDSC and CTD2 database screening revealed that Trametinib demonstrates a significant inhibitory effect on PDAC. We found that Trametinib has a lower IC50 than Gemcitabine in PDAC cell lines. Both Trametinib and Gemcitabine can decrease the proliferation capacity of pancreatic cells, induce cell cycle arrest, and increase apoptosis. Simultaneously, the phosphorylation of the AKT and ERK pathways were inhibited by the treatment of Trametinib. In addition, the RNA-seq of Trametinib-induced resistance PDAC cell lines reveals that the cyclin-dependent kinase (CDK)-RB-E2F regulatory axis and G2/M DNA damage checkpoint might lead the drug resistance. Besides, the combination of Trametinib with Palbociclib could inhibit the proliferation and cell cycle of both resistant cells lines and also restore the sensitivity of drug-resistant cells to Trametinib. Last but not least, the interferon-α and interferon-γ expression were upregulated in resistance cell lines, which might lead to the reversal of drug resistance. The study shows Trametinib has a critical inhibitory effect on PDAC. Besides, the combination of Trametinib with Palbociclib can inhibit the proliferation of PDAC-resistant cells.


Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Gemcitabine , Cell Proliferation , Cell Line, Tumor , Carcinoma, Pancreatic Ductal/drug therapy , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/metabolism , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Cell Cycle , Mitogen-Activated Protein Kinase Kinases , Cyclin-Dependent Kinase 4
18.
Heliyon ; 10(8): e29159, 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38644860

Acute kidney injury (AKI) is a clinical syndrome with high morbidity and mortality caused by various factor. The specific strategies for AKI are still lacking. GSK3ß is widely expressed in the kidneys. In acute models of injury, GSK3ß promotes the systemic inflammatory response, increases the proinflammatory release of cytokines, induces apoptosis, and alters cell proliferation. We screened a series of 3-(4-pyridyl)-5-(4-sulfamido-phenyl)-1,2,4-oxadiazole derivatives which are recognized as new GSK3ß inhibitors, and found that 5n had the least toxicity and the best cell protection. We then tested the anti-inflammatory and reno-protective effect of 5n in cisplatin-treated tubular epithelial cells. 5n had anti-inflammation effect indicated by phosphor-NF-κB detection. Finally, we found that 5n ameliorated renal injury and inflammation in cisplatin-induced AKI mouse model. Silencing GSK3ß inhibited cell injury and inflammation induced by cisplatin. We found that GSK3ß interacted with PP2Ac to modulate the activity of NF-κB. In conclusion, 5n, the novel GSK3ß inhibitor, protects against AKI via PP2Ac-dependent mechanisms which may provide a potential strategy for the treatment of AKI in clinic.

19.
Clin Oral Investig ; 28(5): 244, 2024 Apr 07.
Article En | MEDLINE | ID: mdl-38583113

OBJECTIVES: To compare oral adhesive bandages with the classic compression method and evaluate the clinical efficacy of this wound dressing material in improving postoperative comfort, wound healing, and hemostasis in tooth extraction. MATERIALS AND METHODS: The study was designed as a randomized controlled clinical trial. A total of 120 patients were recruited and randomly assigned to the study group and the control group. In the study group, oral adhesive bandages were used as wound dressing. In the control group, patients bit on cotton balls and gauze, as usual. Hemorrhage, comfort, and healing levels were evaluated at postoperative 1 h, 24 h, and 7 days. The adhesion time of the oral adhesive bandages was also recorded. RESULTS: The average adhesion time of the oral adhesive bandages was 26.6 h. At postoperative 1 and 24 h, the hemostatic levels of the oral adhesive bandage group were significantly higher than those of the control group. The oral adhesive bandage group also reported significantly higher comfort scores than the control group. Both groups had similar healing levels and side effects. But the mean score for wound healing was slightly higher in the oral adhesive bandage group. CONCLUSIONS: Oral adhesive bandages were more effective than cotton balls and gauze in providing hemostatic and comfort effects on extraction wounds. CLINICAL RELEVANCE: Oral adhesive bandages possess clinical value in the management of extraction wounds.


Hemostatics , Humans , Hemostatics/therapeutic use , Bandages , Tooth Extraction , Dental Care , Hemostasis
20.
J Stroke Cerebrovasc Dis ; 33(7): 107737, 2024 Apr 28.
Article En | MEDLINE | ID: mdl-38688395

BACKGROUND: The association between hypothyroidism and stroke remains controversial and the association between hypothyroidism and stroke subtypes has not been satisfactorily researched. This study aimed to explore the causal effect of hypothyroidism on the risk of stroke and its subtypes by Mendelian randomization (MR) analysis. METHODS: Single nucleotide polymorphisms (SNPs) were selected from published genome-wide association studies (GWAS) meta-analysis as instrumental variables (IVs) for hypothyroidism. As outcomes, summary GWAS data for stroke and its subtypes were obtained from two other large GWAS meta-analyses, including any stroke (AS), any ischemic stroke (AIS), large vessel stroke (LAS), cardiogenic embolic stroke (CES), small vessel stroke (SVS), and intracranial hemorrhage (ICH). Univariate Mendelian randomization (UVMR) and multivariate Mendelian randomization (MVMR) were used to assess the causal effect of hypothyroidism on stroke and its subtypes. RESULTS: In UVMR, genetically predicted hypothyroidism was significantly associated with LAS (OR = 1.14, 95CI = 1.02-1.27) and SVS (OR = 1.14, 95CI = 1.04-1.25), but not with AS, AIS, CES, and ICH. The results of the MVMR showed that after adjusting for smoking, alcohol consumption, hypertension, diabetes, low-density lipoprotein cholesterol (LDL-c), and body mass index (BMI), the causal association between hypothyroidism and SVS remained significant, while the association between hypothyroidism and LAS became nonsignificant. CONCLUSION: Hypothyroidism is causally associated with risk for LAS and SVS, but not for other stroke subtypes. Hypothyroidism may be an independent risk factor for SVS, and vascular risk factors play an important role in hypothyroidism causing LAS.

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