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1.
J Ethnopharmacol ; : 118522, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38971345

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Labisia pumila (Blume) Fern.-Vill, also known as Kacip Fatimah, is a traditional medicinal herb common throughout Southeast Asia. It is primarily used to facilitate childbirth and postpartum recovery in women. Additionally, it can also be used to treat dysentery, rheumatism, gonorrhea, and as an anti-flatulent. AIM OF THIS REVIEW: This article aims to provide a comprehensive review of the traditional uses, botany, cultivation, phytochemistry, pharmacological effects, practical applications, and potential uses of L. pumila (LP). Furthermore, we also explore the safety of this plant and its potential prospects for application. MATERIALS AND METHODS: The keywords "Labisia pumila," "Kacip Fatimah," and "Marantodes pumilum" were used to collect relevant information through electronic searches (including Elsevier, PubMed, Google Scholar, Baidu Scholar, CNKI, ScienceDirect, and Web of Science). RESULTS: This review summarizes 102 chemical components from different parts of the plant, including flavonoids, phenolic acids, saponins, and other chemical components. In addition, we also address the associated cultivation conditions, traditional uses, pharmacological effects and toxicity. A large number of reports indicate that LP has various pharmacological effects such as antioxidant, phytoestrogenic, antiinflammtory, antimicrobial, anti-osteoporosis and anti-obesity properties. These results provide valuable references for future research on LP. In addition, LP is also a potential medicinal and edible plant, and is currently sold on the market as a dietary supplement. CONCLUSIONS: LP is a renowned traditional ethnic medicine with numerous pharmacological activities attributed to its bioactive components. Therefore, isolation and identification of the chemical components in LP can be a focus of our future research. Current studies have focused only on the effects of LP on estrogen deficiency-related diseases in women and bone diseases. There is no scientific evidence for other traditional uses. Therefore, it is important to further explore its pharmacological activities and fill the research gaps related to other traditional uses. Furthermore, research on its safety should be expanded to prepare clinical applications.

2.
Front Immunol ; 15: 1425168, 2024.
Article in English | MEDLINE | ID: mdl-38947332

ABSTRACT

C-reactive protein (CRP) is a plasma protein that is evolutionarily conserved, found in both vertebrates and many invertebrates. It is a member of the pentraxin superfamily, characterized by its pentameric structure and calcium-dependent binding to ligands like phosphocholine (PC). In humans and various other species, the plasma concentration of this protein is markedly elevated during inflammatory conditions, establishing it as a prototypical acute phase protein that plays a role in innate immune responses. This feature can also be used clinically to evaluate the severity of inflammation in the organism. Human CRP (huCRP) can exhibit contrasting biological functions due to conformational transitions, while CRP in various species retains conserved protective functions in vivo. The focus of this review will be on the structural traits of CRP, the regulation of its expression, activate complement, and its function in related diseases in vivo.


Subject(s)
C-Reactive Protein , Humans , C-Reactive Protein/metabolism , C-Reactive Protein/immunology , Animals , Inflammation/immunology , Inflammation/metabolism , Immunity, Innate , Protein Conformation , Structure-Activity Relationship , Complement Activation
3.
Angew Chem Int Ed Engl ; : e202404598, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38945836

ABSTRACT

Acetic acid (AA), a vital compound in chemical production and materials manufacturing, is conventionally synthesized by starting with coal or methane through multiple steps including high-temperature transformations. Here we present a new synthesis of AA from ethane through photocatalytic selective oxidation of ethane by H2O2 at 0-25°C. The catalyst designed for this process comprises g-C3N4 with anchored Pd1 single-atom sites. In-situ studies and computational simulation suggest the immobilized Pd1 atom becomes positively charged under photocatalytic condition. Under photoirradiation, the holes on the Pd1 single-atom of OH-Pd1Å/g-C3N4 serves as a catalytic site for activating a C-H instead of C-C of C2H6 with a low activation barrier of 0.14 eV, through a concerted mechanism. Remarkably, the selectivity for synthesizing AA reaches 98.7%, achieved under atmospheric pressure of ethane at 0°C. By integrating photocatalysis with thermal catalysis, we introduce a highly selective, environmentally friendly, energy-efficient synthetic route for AA, starting from ethane, presenting a promising alternative for AA synthesis. This integration of photocatalysis in low-temperature oxidation demonstrates a new route of selective oxidation of light alkanes.

4.
Int J Mol Sci ; 25(12)2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38928160

ABSTRACT

Aflatoxin B1 (AFB1) contamination is a serious threat to nutritional safety and public health. The CotA-laccase from Bacillus licheniformis ANSB821 previously reported by our laboratory showed great potential to degrade AFB1 without redox mediators. However, the use of this CotA-laccase to remove AFB1 in animal feed is limited because of its low catalytic efficiency and low expression level. In order to make better use of this excellent enzyme to effectively degrade AFB1, twelve mutants of CotA-laccase were constructed by site-directed mutagenesis. Among these mutants, E186A and E186R showed the best degradation ability of AFB1, with degradation ratios of 82.2% and 91.8% within 12 h, which were 1.6- and 1.8-times higher than those of the wild-type CotA-laccase, respectively. The catalytic efficiencies (kcat/Km) of E186A and E186R were found to be 1.8- and 3.2-times higher, respectively, than those of the wild-type CotA-laccase. Then the expression vectors pPICZαA-N-E186A and pPICZαA-N-E186R with an optimized signal peptide were constructed and transformed into Pichia pastoris GS115. The optimized signal peptide improved the secretory expressions of E186A and E186R in P. pastoris GS115. Collectively, the current study provided ideal candidate CotA-laccase mutants for AFB1 detoxification in food and animal feed and a feasible protocol, which was desperately needed for the industrial production of CotA-laccases.


Subject(s)
Aflatoxin B1 , Bacillus licheniformis , Bacterial Proteins , Laccase , Aflatoxin B1/metabolism , Bacillus licheniformis/genetics , Bacillus licheniformis/metabolism , Bacillus licheniformis/enzymology , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Laccase/metabolism , Laccase/genetics , Mutagenesis, Site-Directed , Recombinant Proteins/metabolism , Recombinant Proteins/genetics , Saccharomycetales
5.
Toxicol Appl Pharmacol ; 488: 116980, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38823456

ABSTRACT

Multiple sclerosis (MS) is a class of autoimmune diseases mainly caused by the immune system attacking the myelin sheath of the axons in the nervous system. Although the pathogenesis of MS is complex, studies have shown that dendritic cells (DCs) play a vital role in the pathogenesis of MS. Quercetin (QU) has a unique advantage in clinical application, especially for treating autoimmune diseases. However, the mechanism of QU in the treatment of experimental autoimmune encephalomyelitis (EAE) remains unclear. In this study, we explore the potential role of QU in EAE. Finally, we find that QU has anti-inflammatory activities and neural protective effects in EAE. The experimental results suggest that the cellular basis for QU's function is to inhibit the activation of DCs while modulating the Th17 cell differentiation in the co-culture system. Further, QU may target STAT4 to inhibit its activation in DCs. This work will be of great significance for the future development and utilization of QU.


Subject(s)
Dendritic Cells , Encephalomyelitis, Autoimmune, Experimental , Mice, Inbred C57BL , Quercetin , STAT4 Transcription Factor , Th17 Cells , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Encephalomyelitis, Autoimmune, Experimental/immunology , Encephalomyelitis, Autoimmune, Experimental/metabolism , Dendritic Cells/drug effects , Dendritic Cells/immunology , Dendritic Cells/metabolism , Animals , Quercetin/pharmacology , STAT4 Transcription Factor/metabolism , Female , Mice , Th17 Cells/drug effects , Th17 Cells/immunology , Th17 Cells/metabolism , Cell Differentiation/drug effects , Coculture Techniques , Anti-Inflammatory Agents/pharmacology
6.
Curr Med Sci ; 44(3): 554-560, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38842773

ABSTRACT

OBJECTIVE: This study aimed to compare the performance of standard-definition white-light endoscopy (SD-WL), high-definition white-light endoscopy (HD-WL), and high-definition narrow-band imaging (HD-NBI) in detecting colorectal lesions in the Chinese population. METHODS: This was a multicenter, single-blind, randomized, controlled trial with a non-inferiority design. Patients undergoing endoscopy for physical examination, screening, and surveillance were enrolled from July 2017 to December 2020. The primary outcome measure was the adenoma detection rate (ADR), defined as the proportion of patients with at least one adenoma detected. The associated factors for detecting adenomas were assessed using univariate and multivariate logistic regression. RESULTS: Out of 653 eligible patients enrolled, data from 596 patients were analyzed. The ADRs were 34.5% in the SD-WL group, 33.5% in the HD-WL group, and 37.5% in the HD-NBI group (P=0.72). The advanced neoplasm detection rates (ANDRs) in the three arms were 17.1%, 15.5%, and 10.4% (P=0.17). No significant differences were found between the SD group and HD group regarding ADR or ANDR (ADR: 34.5% vs. 35.6%, P=0.79; ANDR: 17.1% vs. 13.0%, P=0.16, respectively). Similar results were observed between the HD-WL group and HD-NBI group (ADR: 33.5% vs. 37.7%, P=0.45; ANDR: 15.5% vs. 10.4%, P=0.18, respectively). In the univariate and multivariate logistic regression analyses, neither HD-WL nor HD-NBI led to a significant difference in overall adenoma detection compared to SD-WL (HD-WL: OR 0.91, P=0.69; HD-NBI: OR 1.15, P=0.80). CONCLUSION: HD-NBI and HD-WL are comparable to SD-WL for overall adenoma detection among Chinese outpatients. It can be concluded that HD-NBI or HD-WL is not superior to SD-WL, but more effective instruction may be needed to guide the selection of different endoscopic methods in the future. Our study's conclusions may aid in the efficient allocation and utilization of limited colonoscopy resources, especially advanced imaging technologies.


Subject(s)
Adenoma , Colonoscopy , Colorectal Neoplasms , Narrow Band Imaging , Humans , Male , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/diagnosis , Female , Middle Aged , Adenoma/diagnostic imaging , Adenoma/diagnosis , Narrow Band Imaging/methods , Colonoscopy/methods , Aged , Single-Blind Method , Light , Adult
7.
Phytochemistry ; 225: 114198, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38936528

ABSTRACT

Three previously undescribed and sixteen known alkaloids were bioguidedly isolated from the bulbs of Narcissus tazetta subsp. chinensis (M.Roem.) Masamura & Yanagih. The structures were elucidated by spectroscopic data, including HRESIMS, NMR, and ECD. Eleven of the isolated alkaloids exhibited immunosuppressive activity on the proliferation of human T cells. (+)-Narciclasine (18) showed the most significantly suppressive activity with an IC50 value of 14 ± 5 nM. In vitro, (+)-narciclasine (18) blocked NF-κB signal transduction, but did not affect PI3K/AKT signal transduction. What was more, (+)-narciclasine significantly reduced ALT and AST levels and alleviated liver damage induced by ConA in AIH mouse model.

8.
Int J Mol Sci ; 25(11)2024 May 27.
Article in English | MEDLINE | ID: mdl-38892000

ABSTRACT

Paclitaxel, a microtubule-stabilizing chemotherapy drug, can cause severe paclitaxel-induced peripheral neuropathic pain (PIPNP). The roles of transient receptor potential (TRP) ion channel vanilloid 1 (TRPV1, a nociceptor and heat sensor) and melastatin 8 (TRPM8, a cold sensor) in PIPNP remain controversial. In this study, Western blotting, immunofluorescence staining, and calcium imaging revealed that the expression and functional activity of TRPV1 were upregulated in rat dorsal root ganglion (DRG) neurons in PIPNP. Behavioral assessments using the von Frey and brush tests demonstrated that mechanical hyperalgesia in PIPNP was significantly inhibited by intraperitoneal or intrathecal administration of the TRPV1 antagonist capsazepine, indicating that TRPV1 played a key role in PIPNP. Conversely, the expression of TRPM8 protein decreased and its channel activity was reduced in DRG neurons. Furthermore, activation of TRPM8 via topical application of menthol or intrathecal injection of WS-12 attenuated the mechanical pain. Mechanistically, the TRPV1 activity triggered by capsaicin (a TRPV1 agonist) was reduced after menthol application in cultured DRG neurons, especially in the paclitaxel-treated group. These findings showed that upregulation of TRPV1 and inhibition of TRPM8 are involved in the generation of PIPNP, and they suggested that inhibition of TRPV1 function in DRG neurons via activation of TRPM8 might underlie the analgesic effects of menthol.


Subject(s)
Ganglia, Spinal , Neuralgia , Paclitaxel , Rats, Sprague-Dawley , TRPM Cation Channels , TRPV Cation Channels , Animals , Paclitaxel/adverse effects , Paclitaxel/pharmacology , TRPM Cation Channels/metabolism , TRPV Cation Channels/metabolism , Ganglia, Spinal/metabolism , Ganglia, Spinal/drug effects , Rats , Neuralgia/metabolism , Neuralgia/drug therapy , Neuralgia/chemically induced , Male , Hyperalgesia/metabolism , Hyperalgesia/chemically induced , Hyperalgesia/drug therapy , Capsaicin/pharmacology , Capsaicin/analogs & derivatives , Neurons/metabolism , Neurons/drug effects
9.
Nephrology (Carlton) ; 2024 Jun 09.
Article in English | MEDLINE | ID: mdl-38852614

ABSTRACT

Unilateral kidney hypoplasia is a congenital condition characterized by the underdevelopment of one kidney. Although often asymptomatic, it can cause severe renal complications in patients combined with contralateral renal injury, leading to acute renal failure. This case report describes a patient with unilateral kidney hypoplasia who underwent a kidney biopsy on the contralateral normal-sized kidney and subsequently developed oliguric acute kidney injury. This report discusses the challenges encountered while diagnosing and managing this rare case, highlighting the importance of awareness and recognition to perform timely intervention and optimize the patient's outcome.

10.
Article in English | MEDLINE | ID: mdl-38870512

ABSTRACT

Objective: This study aims to evaluate the efficiency of ultrasound-guided core needle biopsy (CNB) and fine needle aspiration biopsy (FNA) in the diagnosis of breast cancer with internal mammary node (IMN) metastasis. The focus is on specimen satisfaction, puncture tolerance, and classification accuracy. Methods: A retrospective analysis was conducted on breast cancer patients (n=106) who underwent ultrasound-guided IMN biopsy at our hospital from March 2020 to March 2023. Patients were divided into CNB and FNA groups based on the biopsy technique. The study analyzed one-time sampling satisfaction, overall specimen satisfaction, and post-puncture pain score (VAS), comparing the effectiveness of both methods in IMN diagnosis and classification. Results: In the CNB and FNA groups, 3 and 1 cases respectively had unsatisfactory specimens, later excluded in pathological examinations. The FNA group demonstrated higher one-time sampling satisfaction than the CNB group (P < .05), but no significant difference in overall specimen satisfaction was observed (P > .05). Among 102 patients with satisfactory specimens, 96 showed positive IMN metastasis. The kappa statistics measuring the consistency between biopsy methods and actual IMN (Invasive Mammary Carcinoma) metastasis show a value of 0.637 for CNB (Core Needle Biopsy) and 0.769 for FNA (Fine Needle Aspiration), indicating a higher consistency for FNA. Different IMN types also varied in kappa values. Post-puncture VAS scores were higher in the CNB group (P < .05), with no significant difference in total complication rates between the groups (P > .05). Conclusion: Ultrasound-guided CNB and FNA both demonstrate good overall specimen satisfaction and equivalent safety. FNA. However, FNA showed superior performance in one-time specimen satisfaction, diagnostic consistency for IMN metastasis, and patient tolerance during the procedure.

11.
Cancer Cell Int ; 24(1): 207, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38867223

ABSTRACT

BACKGROUND: Globally, breast cancer in women is the fifth leading cause of cancer death. There is an urgent need to explore the molecular mechanism of breast cancer proliferation and metastasis. METHOD: TCGA database analysis was used to analyze genes expression in breast cancer and normal samples and the association between gene expression and prognosis. Immunohistochemical staining, qPCR and western blotting was sued to detected gene expression. The cell function tests were conducted to investigate the effects of TEX19 and CDK4 with abnormal expression on cell proliferation, migration, apoptosis, cell cycle, and colony formation. Bioinformatics analysis methods combined with CHX tracking experiment and Co-IP experiment were performed to screen and verify the downstream molecule and regulatory mechanism of TEX19. Besides, subcutaneous tumorigenesis model in nude mice was constructed. RESULTS: TEX19 was significantly upregulated in breast cancer, and the TEX19 level was related to tumor invasion and prognosis. TEX19 knockdown inhibited the proliferation and migration of breast cancer cells, increased cell apoptosis, and blocked the cell cycle in the G2 phase. Besides, TEX19 suppressed the growth of tumors in the body. Mechanically, TEX19 upregulated the level of CDK4 protein, which depended on the E3 ubiquitin ligase SKP2. Specifically, TEX19 knockdown and SKP2 protein overexpression destroyed the stability of CDK4 protein and enhanced the ubiquitination of CDK4 protein. Additionally, CDK4 knockdown inhibited the proliferation, migration, and colony formation of breast cancer cells, and alleviated the promotion of TEX19 overexpression on the proliferation and migration of breast cancer cell. CONCLUSION: TEX19 and CDK4 were upregulated in breast cancer, and TEX19 increased the level of CDK4 protein by influencing SKP2-mediated ubiquitination of CDK4, thereby promoting the progression of breast cancer.

12.
Fa Yi Xue Za Zhi ; 40(2): 135-142, 2024 Apr 25.
Article in English, Chinese | MEDLINE | ID: mdl-38847027

ABSTRACT

OBJECTIVES: To investigate the application value of combining the Demirjian's method with machine learning algorithms for dental age estimation in northern Chinese Han children and adolescents. METHODS: Oral panoramic images of 10 256 Han individuals aged 5 to 24 years in northern China were collected. The development of eight permanent teeth in the left mandibular was classified into different stages using the Demirjian's method. Various machine learning algorithms, including support vector regression (SVR), gradient boosting regression (GBR), linear regression (LR), random forest regression (RFR), and decision tree regression (DTR) were employed. Age estimation models were constructed based on total, female, and male samples respectively using these algorithms. The fitting performance of different machine learning algorithms in these three groups was evaluated. RESULTS: SVR demonstrated superior estimation efficiency among all machine learning models in both total and female samples, while GBR showed the best performance in male samples. The mean absolute error (MAE) of the optimal age estimation model was 1.246 3, 1.281 8 and 1.153 8 years in the total, female and male samples, respectively. The optimal age estimation model exhibited varying levels of accuracy across different age ranges, which provided relatively accurate age estimations in individuals under 18 years old. CONCLUSIONS: The machine learning model developed in this study exhibits good age estimation efficiency in northern Chinese Han children and adolescents. However, its performance is not ideal when applied to adult population. To improve the accuracy in age estimation, the other variables can be considered.


Subject(s)
Age Determination by Teeth , Algorithms , Asian People , Machine Learning , Radiography, Panoramic , Humans , Adolescent , Child , Male , Female , Age Determination by Teeth/methods , Radiography, Panoramic/methods , China/ethnology , Child, Preschool , Young Adult , Mandible , Tooth/diagnostic imaging , Tooth/growth & development , Support Vector Machine , Decision Trees , Ethnicity , East Asian People
13.
Nanotechnology ; 35(36)2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38848693

ABSTRACT

Aqueous aluminum-ion batteries have many advantages such as their safety, environmental friendliness, low cost, high reserves and the high theoretical specific capacity of aluminum. So aqueous aluminum-ion batteries are potential substitute for lithium-ion batteries. In this paper, the current research status and development trends of cathode and anode materials and electrolytes for aqueous aluminum-ion batteries are described. Aiming at the problem of passivation, corrosion and hydrogen evolution reaction of aluminum anode and dissolution and irreversible change of cathode after cycling in aqueous aluminum-ion batteries. Solutions of different research routes such as ASEI (artificial solid electrolyte interphase), alloying, amorphization, elemental doping, electrolyte regulation, etc and different transformation mechanisms of anode and cathode materials during cycling have been summarized. Moreover, it looks forward to the possible research directions of aqueous aluminum-ion batteries in the future. We hope that this review can provide some insights and support for the design of more suitable electrode materials and electrolytes for aqueous aluminum-ion batteries.

14.
Eur J Med Res ; 29(1): 321, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38858735

ABSTRACT

BACKGROUND: Migraine, as a prevalent neurologic disorder, involves intricate and yet incompletely elucidated pathophysiological mechanisms. A plethora of research findings underscores the pivotal role played by astrocytes in the progression of migraines. In order to elucidate the current advances and directions in research pertaining to astrocytes in migraines, we conducted bibliometric analysis of relevant literature and visualized the results. Subsequently, we expound upon these findings to contribute to the evolving understanding of the role of astrocytes in migraine pathophysiology. METHODS: On November 21, 2023, we conducted a search on Web of Science (WOS), restricting the document type to articles or reviews and language to English. Following a meticulous selection process involving three researchers, we identified the literature to be included in our analysis. Subsequently, we employed Microsoft Office Excel programs, R, VOSviewer, Scimago Graphica, and CiteSpace software to conduct visualization analysis of basic information and trends regarding journals, countries/regions, and influential authors, institutions, keywords, and papers. RESULTS: As of November 21, 2023, relevant literature has been published in 71 journals across 27 countries/regions. This corpus comprises contributions from 576 authors affiliated with 220 institutions, encompassing 865 keywords and referencing 6065 scholarly articles. CEPHALALGIA stands out as the most influential journal in this field, while authors PIETROBON D and DALKARA T have significant impact. The United States is highly influential, with CNR and UNIV PADUA emerging as highly influential institutions. The predominant category is Neurosciences. CONCLUSIONS: Future investigators may continue to focus on migraines with aura, familial hemiplegic migraine (FHM), and the crucial calcitonin gene-related peptide (CGRP) system. Employing advanced observational techniques, such as imaging, researchers should pay attention to cellular and tissue structures, such as microglia and the trigeminal ganglion, as well as mechanisms involving inflammation and central sensitization. Moreover, animal models are paramount in obtaining high-quality evidence.


Subject(s)
Astrocytes , Bibliometrics , Migraine Disorders , Humans , Astrocytes/pathology
15.
Appl Opt ; 63(12): 3228-3236, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38856471

ABSTRACT

Due to its numerous advantages such as high gain and low operating bias, the silicon photomultiplier (SiPM) holds great potential in LiDAR applications. However, it is more jittery at weak echoes and more sensitive to ambient light, making its ranging performance at low signal-to-noise ratios (SNRs) severely deteriorated. To enhance the ranging performance of SiPM LiDAR under low SNR, a novel echo processing method, to the best of our knowledge, was proposed based on the statistical property of SiPM responses and validated under relatively intensive sunlight (>50k l x) using a self-developed LiDAR system. At the same time, laser pulse width modulation and multi-pulse laser emission are used in ranging experiments to maximize the advantages of this method. It has shown that increasing the laser pulse width within a certain range can improve ranging performance, and that emitting multiple laser pulses improves ranging performance more significantly. Utilizing a three-pulse laser with a peak power of only 3.2 W, a target 122 m away was ranged with a precision of 6.53 cm with only five accumulations.

16.
Appl Opt ; 63(15): 4219-4225, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38856516

ABSTRACT

We propose a method using electromagnetically induced transparency (EIT) to measure the frequency offset of the laser relative to a cavity's resonance frequency, thereby reducing the laser detuning when preparing Rydberg atoms. Laser reflection by the vapor cell enables observation of two EIT peaks corresponding to the co-propagating and counter-propagating beams, and the peaks' position is related to laser detuning, allowing us to estimate the frequency offset of the probe and coupling lasers. The method reduces the measurement uncertainty compared to directly observing saturated absorption spectroscopy (SAS) and EIT, making it suitable for applications that require strict control over laser detuning.

17.
Cancer Immunol Immunother ; 73(8): 151, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38832951

ABSTRACT

BACKGROUND: Immunotherapy for gastric cancer remains a challenge due to its limited efficacy. Metabolic reprogramming toward glycolysis has emerged as a promising avenue for enhancing the sensitivity of tumors to immunotherapy. Pyruvate dehydrogenase kinases (PDKs) play pivotal roles in regulating glycolysis. The importance of PDKs in the context of gastric cancer immunotherapy and their potential as therapeutic targets have not been fully explored. METHODS: PDK and PD-L1 expression was analyzed using data from the GSE66229 and The Cancer Genome Atlas (TCGA) cohorts. Additionally, the Immune Checkpoint Blockade Therapy Atlas (ICBatlas) database was utilized to assess PDK expression in an immune checkpoint blockade (ICB) therapy group. Subsequently, the upregulation of PD-L1 and the enhancement of anticancer effects achieved by targeting PDK were validated through in vivo and in vitro assays. The impact of PDK on histone acetylation was investigated using ChIP‒qPCR to detect changes in histone acetylation levels. RESULTS: Our analysis revealed a notable negative correlation between PD-L1 and PDK expression. Downregulation of PDK led to a significant increase in PD-L1 expression. PDK inhibition increased histone acetylation levels by promoting acetyl-CoA generation. The augmentation of acetyl-CoA production and concurrent inhibition of histone deacetylation were found to upregulate PD-L1 expression in gastric cancer cells. Additionally, we observed a significant increase in the anticancer effect of PD-L1 antibodies following treatment with a PDK inhibitor. CONCLUSIONS: Downregulation of PDK in gastric cancer cells leads to an increase in PD-L1 expression levels, thus potentially improving the efficacy of PD-L1 immune checkpoint blockade therapy.


Subject(s)
B7-H1 Antigen , Glycolysis , Immunotherapy , Pyruvate Dehydrogenase Acetyl-Transferring Kinase , Stomach Neoplasms , Up-Regulation , B7-H1 Antigen/metabolism , Humans , Animals , Pyruvate Dehydrogenase Acetyl-Transferring Kinase/metabolism , Pyruvate Dehydrogenase Acetyl-Transferring Kinase/genetics , Stomach Neoplasms/metabolism , Stomach Neoplasms/immunology , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics , Immunotherapy/methods , Mice , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Xenograft Model Antitumor Assays , Mice, Nude
18.
Curr Pharm Des ; 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38867534

ABSTRACT

BACKGROUND: Colorectal Cancer (CRC) is one of the top three malignancies with the highest incidence and mortality. OBJECTIVE: The study aimed to identify the effect of Traditional Chinese Medicine (TCM) on postoperative patients with stage II-III CRC and explore the core herb combination and its mechanism. METHODS: An observational cohort study was conducted on patients diagnosed with stage II-III CRC from January 2016 to January 2021. The primary outcome was disease-free survival, which was compared between the patients who received TCM or not, and the secondary outcome was the hazard ratio. The relevance principle was used to obtain the candidate herb combinations, and the core combination was evaluated through an assessment of efficacy and representativeness. Then, biological processes and signaling pathways associated with CRC were obtained by Gene Ontology function, Kyoto Encyclopedia of Gene and Genomes pathway, and Wikipathway. Furthermore, hub genes were screened by the Kaplan-Meier estimator, and molecular docking was employed to predict the binding sites of key ingredients to hub genes. The correlation analysis was employed for the correlations between the hub genes and tumor-infiltrating immune cells and hypoxiarelated genes. Ultimately, a quantitative polymerase chain reaction was performed to verify the regulation of hub genes by their major ingredients. RESULTS: A total of 707 patients were included. TCM could decrease the metastatic recurrence associated with stage II-III CRC (HR: 0.61, log-rank P < 0.05). Among those patients in the TCM group, the core combination was Baizhu → Yinchen, Chenpi, and Fuling (C combination), and its antitumor mechanism was most likely related to the regulation of BCL2L1, XIAP, and TOP1 by its key ingredients, quercetin and tangeretin. The expression of these genes was significantly correlated with both tumor-infiltrating immune cells and hypoxia- related genes. In addition, quercetin and tangeretin down-regulated the mRNA levels of BCL2L1, XIAP, and TOP1, thereby inhibiting the growth of HCT116 cells. CONCLUSION: Overall, a combination of four herbs, Baizhu → Yinchen, Chenpi, and Fuling, could reduce metastatic recurrence in postoperative patients with stage II-III CRC. The mechanism may be related to the regulation of BCL2L1, XIAP, and TOP1 by its key ingredients quercetin and tangeretin.

19.
Dent Mater ; 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38871526

ABSTRACT

OBJECTIVE: Investigate the bioactivity and stability of Rhodiola rosea (RR) fractions as a natural source of prodelphinidin gallate (PDg) on dentin collagen via analysis of the viscoelastic and resin-dentin adhesive properties of the dentin matrix. METHODS: The biomimicry and stability of RR subfractions (F1, F2, F3 and F4) with collagen were determined by dynamic mechanical analysis (DMA). DMA used a strain sweep method to assess the dentin matrix viscoelastic properties [storage (E'), loss (E"), and complex (E*) moduli and tan δ] after treatment, 7-, 30- and 90-days of storage in simulated body fluids (SBF). Resin-dentin interface properties were assessed after 1 and 90-days in SBF by microtensile bond strength test and confocal laser scanning microscopy. Data were analyzed using two and one-way ANOVA and post-hoc tests (α = 0.05). RESULTS: RR fractions increased dentin matrix complex (96 - 69 MPa) and storage (95 - 68 MPa) moduli, compared to the control (∼9 MPa) in the ranking order: F2 ≥ F3 = F1 = F4 > control (p < 0.001). Treatment did not affect tan δ values. After 30- and 90-days, RR-treated dentin E*, E' and tan δ decreased (p < 0.001). F2 fraction yielded the highest microtensile bond strength (43.9 MPa), compared to F1, F4 (35.9 - 31.7 MPa), and control (29 MPa). RR-treated interfaces mediated stable surface modifications and enhanced collagen-methacrylate resin interactions at the bioadhesive interface. SIGNIFICANCE: Prodelphinidin gallates from RR are potent and reasonably stable biomimetic agents to dentin. Higher potency of F2 fraction with the dentin matrix and the adhesive interface is associated with a degree of polymerization of 2-3 and gallo(yl) motifs.

20.
Sci Rep ; 14(1): 13664, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38871778

ABSTRACT

We exploit bias polarity dependent low-frequency noise (LFN) spectroscopy to investigate charge transport dynamics in ultra-thin AlOx-based magnetic tunnel junctions (MTJs) with bipolar resistive switching (RS). By measuring the noise characteristics across the entire bias voltage range of bipolar RS, we find that the voltage noise level exhibits an bias polarity dependence. This distinct feature is intimately correlated with reconfiguring of the inherently existing oxygen vacancies ( V O . . ) in as-grown MTJ devices during the SET and RESET switching processes. In addition, we observe two-level random telegraph noise (RTN) with a longer and shorter tunneling length in the high resistance state (HRS) and low resistance state (LRS) at a low bias voltage. The intrinsic voltage fluctuations of RTN arise from the dynamics of electron trapping/de-trapping processes at the V O . . -related trap sites. Notably, the RTN magnitude is similar in LRS but nonidentical in that of HRS for different bias polarity. These findings strongly suggest that the inherent V O . . are distributed near the top CoFe/AlOx interface in the HRS; in contrast, they are expanded to the middle region of the AlOx in the LRS. More importantly, we demonstrate that the location and distribution of the inherent V O . . can be electrically tuned, which plays an essential role in the charge transport dynamics in the ultra-thin AlOx-based MTJs and have significant implications for developing emergent memory and logic devices.

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