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1.
World J Diabetes ; 15(6): 1162-1177, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38983804

ABSTRACT

Diabetic foot ulcers (DFUs) pose a critical medical challenge, significantly im-pairing the quality of life of patients. Adipose-derived stem cells (ADSCs) have been identified as a promising therapeutic approach for improving wound healing in DFUs. Despite extensive exploration of the mechanical aspects of ADSC therapy against DFU, its clinical applications remain elusive. In this review, we aimed to bridge this gap by evaluating the use and advancements of ADSCs in the clinical management of DFUs. The review begins with a discussion of the classification and clinical management of diabetic foot conditions. It then discusses the current landscape of clinical trials, focusing on their geographic distribution, reported efficacy, safety profiles, treatment timing, administration techniques, and dosing considerations. Finally, the review discusses the preclinical strategies to enhance ADSC efficacy. This review shows that many trials exhibit biases in study design, unclear inclusion criteria, and intervention protocols. In conclusion, this review underscores the potential of ADSCs in DFU treatment and emphasizes the critical need for further research and refinement of therapeutic approaches, with a focus on improving the quality of future clinical trials to enhance treatment outcomes and advance the field of diabetic wound care.

2.
Exp Eye Res ; 246: 109990, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38969283

ABSTRACT

Ocular melanoma, including uveal melanoma (UM) and conjunctival melanoma (CM), is the most common ocular cancer among adults with a high rate of recurrence and poor prognosis. Loss of epigenetic homeostasis disturbed gene expression patterns, resulting in oncogenesis. Herein, we comprehensively analyzed the DNA methylation, transcriptome profiles, and corresponding clinical information of UM patients through multiple machine-learning algorithms, finding that a methylation-driven gene RBMS1 was correlated with poor clinical outcomes of UM patients. RNA-seq and single-cell RNA-seq analyses revealed that RBMS1 reflected diverse tumor microenvironments, where high RBMS1 expression marked an immune active TME. Furthermore, we found that tumor cells were identified to have the higher communication probability in RBMS1+ state. The functional enrichment analysis revealed that RBMS1 was associated with pigment granule and melanosome, participating in cell proliferation as well as apoptotic signaling pathway. Biological experiments were performed and demonstrated that the silencing of RBMS1 inhibited ocular melanoma proliferation and promoted apoptosis. Our study highlighted that RBMS1 reflects a distinct microenvironment and promotes tumor progression in ocular melanoma, contributing to the therapeutic customization and clinical decision-making.

3.
Small ; : e2404402, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38963075

ABSTRACT

Developing multifunctional, stimuli-responsive nanomedicine is intriguing because it has the potential to effectively treat cancer. Yet, poor tumor penetration of nanodrugs results in limited antitumor efficacy. Herein, an oxygen-driven silicon-based nanomotor (Si-motor) loaded with MnO and CaO2 nanoparticles is developed, which can move in tumor microenvironment (TME) by the cascade reaction of CaO2 and MnO. Under acidic TME, CaO2 reacts with acid to release Ca2+ to induce mitochondrial damage and simultaneously produces O2 and H2O2, when the loaded MnO exerts Fenton-like activity to produce ·OH and O2 based on the produced H2O2. The generated O2 drives Si-motor forward, thus endowing active delivery capability of the formed motors in TME. Meanwhile, MnO with glutathione (GSH) depletion ability further prevents reactive oxygen species (ROS) from being destroyed. Such TME actuated Si-motor with enhanced cellular uptake and deep penetration provides amplification of synergistic oxidative stresscaused by intracellular Ca2 + overloading, GSH depletion induced by Mn2+, and Mn2+ mediated chemodynamic treatment (CDT), leading to excellent tumor cell death. The created nanomotor may offer an effective platform for active synergistic cancer treatment.

4.
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
5.
Sensors (Basel) ; 24(13)2024 Jun 30.
Article in English | MEDLINE | ID: mdl-39001043

ABSTRACT

The properties of nanopipettes largely rely on the materials introduced onto their inner walls, which allow for a vast extension of their sensing capabilities. The challenge of simultaneously enhancing the sensitivity and selectivity of nanopipettes for pH sensing remains, hindering their practical applications. Herein, we report insulin-modified nanopipettes with excellent pH response performances, which were prepared by introducing insulin onto their inner walls via a two-step reaction involving silanization and amidation. The pH response intensity based on ion current rectification was significantly enhanced by approximately 4.29 times when utilizing insulin-modified nanopipettes compared with bare ones, demonstrating a linear response within the pH range of 2.50 to 7.80. In addition, insulin-modified nanopipettes featured good reversibility and selectivity. The modification processes were monitored using the I-V curves, and the relevant mechanisms were discussed. The effects of solution pH and insulin concentration on the modification results were investigated to achieve optimal insulin introduction. This study showed that the pH response behavior of nanopipettes can be greatly improved by introducing versatile molecules onto the inner walls, thereby contributing to the development and utilization of pH-responsive nanopipettes.


Subject(s)
Insulin , Hydrogen-Ion Concentration , Insulin/chemistry , Biosensing Techniques/methods , Ions/chemistry
6.
Food Chem X ; 23: 101556, 2024 Oct 30.
Article in English | MEDLINE | ID: mdl-39007118

ABSTRACT

This study aimed to identify the key volatile compounds in two types of processed arabica coffee husk tea, elucidate their olfactory characteristics, and investigate their antioxidant and anti-inflammatory activities. Sensory evaluation indicated differences between the two groups. A total of 64 and 99 compounds were identified in the C and FC groups, respectively, with 5 identified as key aroma compounds (ROAV≥1). Molecular simulations indicated that four common key aroma compounds were successfully docked with OR1A1 and OR5M3 receptors, forming stable complexes. Furthermore, 14 volatile compounds interacted with 140 targets associated with oxidation and inflammation, linking to 919 gene ontology (GO) terms and 135 kyoto encyclopedia of genes and genomes (KEGG) pathways. Molecular simulations revealed that these volatile components showed antioxidant and anti-inflammatory effects by interacting with core receptors through several forces, including van der Waals, Pi-alkyl, and Pi-cation interactions and hydrogen bonds.

7.
Brain Res Bull ; : 111031, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-39002935

ABSTRACT

We have previously reported that the expression of miR-34c-5p was up-regulated during acupuncture treatment in the setting of a cerebral ischemia/reperfusion injury (CIRI), indicating that miR-34c-5p plays an important role in healing from a CIRI-induced brain injury. This study sought to evaluate the effects of acupuncture on miR-34c-5p expression and autophagy in the forward and reverse directions using a rat focal cerebral ischemia/reperfusion model. After 120minutes of middle cerebral artery occlusion and reperfusion, rats were treated with acupuncture at the "Dazhui" (DU20), "Baihui" (DU26) and "Renzhong" (DU14) points. Neurologic function deficit score, cerebral infarct area ratio, neuronal apoptosis and miR-34c-5p expression were evaluated 72hr after treatment. The autophagy agonist RAPA and the antagonist 3MA were used to evaluate the neuro protective effects of autophagy-mediated acupuncture. We found that acupuncture treatment improved autophagy in the brain tissue of CIRI rats. Acupuncture reversed the negative effects of 3MA on CIRI, and acupuncture combined with RAPA further enhanced autophagy. We also found that acupuncture could increase miR-34c-5p expression in hippocampal neurons after ischemia/reperfusion. Acupuncture and a miR-34c agomir were able to enhance autophagy, improve neurologic deficits, and reduce the cerebral infarct area ratio and apoptosis rate by promoting the expression of miR-34c-5p. Silencing miR-34c resulted in a significantly reduced activating effect of acupuncture on autophagy and increased apoptosis, neurologic deficit symptoms, and cerebral infarct area ratio. This confirms that acupuncture can upregulate miR-34c-5p expression, which is beneficial in the treatment of CIRI.

8.
Gut ; 2024 Jul 13.
Article in English | MEDLINE | ID: mdl-38960582

ABSTRACT

OBJECTIVE: Our study aimed to explore the influence of gut microbiota and their metabolites on intracranial aneurysms (IA) progression and pinpoint-related metabolic biomarkers derived from the gut microbiome. DESIGN: We recruited 358 patients with unruptured IA (UIA) and 161 with ruptured IA (RIA) from two distinct geographical regions for conducting an integrated analysis of plasma metabolomics and faecal metagenomics. Machine learning algorithms were employed to develop a classifier model, subsequently validated in an independent cohort. Mouse models of IA were established to verify the potential role of the specific metabolite identified. RESULTS: Distinct shifts in taxonomic and functional profiles of gut microbiota and their related metabolites were observed in different IA stages. Notably, tryptophan metabolites, particularly indoxyl sulfate (IS), were significantly higher in plasma of RIA. Meanwhile, upregulated tryptophanase expression and indole-producing microbiota were observed in gut microbiome of RIA. A model harnessing gut-microbiome-derived tryptophan metabolites demonstrated remarkable efficacy in distinguishing RIA from UIA patients in the validation cohort (AUC=0.97). Gut microbiota depletion by antibiotics decreased plasma IS concentration, reduced IA formation and rupture in mice, and downregulated matrix metalloproteinase-9 expression in aneurysmal walls with elastin degradation reduction. Supplement of IS reversed the effect of gut microbiota depletion. CONCLUSION: Our investigation highlights the potential of gut-microbiome-derived tryptophan metabolites as biomarkers for distinguishing RIA from UIA patients. The findings suggest a novel pathogenic role for gut-microbiome-derived IS in elastin degradation in the IA wall leading to the rupture of IA.

9.
Sci Rep ; 14(1): 16233, 2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39004658

ABSTRACT

Saline-sodic stress restricts the absorption of zinc by rice, consequently impacting the photosynthesis process of rice plants. In this experiment, Landrace 9 was selected as the test material and the potting method was employed to investigate the influence of ZnO nanoparticles (ZnO NPs) on zinc absorption and chlorophyll fluorescence in rice grown in saline-sodic land. The research findings demonstrate that the application of ZnO NPs proves to be more advantageous for the growth of rice in saline-sodic soil. Notably, the application of ZnO NPs significantly decreases the levels of Na+ and MDA in rice leaves in saline-sodic soil, while increasing the levels of K+ and Zn2+. Additionally, ZnO NPs enhances the content of chloroplast pigments, specific energy flux, quantum yield, and the performance of active PSII reaction center (PIABS) in rice leaves under saline-sodic stress. Furthermore, the relative variable fluorescence (WK and VJ) and quantum energy dissipation rate (φDo) of rice are also reduced. Therefore, the addition of ZnO NPs enhances the transfer of electrons and energy within the rice photosystem when subjected to saline-sodic stress. This promotes photosynthesis in rice plants growing in saline-sodic land, increasing their resistance to saline-sodic stress and ultimately facilitating their growth and development.


Subject(s)
Oryza , Photosynthesis , Plant Leaves , Soil , Zinc Oxide , Oryza/metabolism , Oryza/drug effects , Oryza/growth & development , Zinc Oxide/pharmacology , Photosynthesis/drug effects , Plant Leaves/metabolism , Plant Leaves/drug effects , Soil/chemistry , Chlorophyll/metabolism , Photosystem II Protein Complex/metabolism , Metal Nanoparticles/chemistry , Fluorescence , Salinity
10.
PeerJ Comput Sci ; 10: e2048, 2024.
Article in English | MEDLINE | ID: mdl-38855216

ABSTRACT

In the quest for sustainable urban development, precise quantification of urban green space is paramount. This research delineates the implementation of a Cosine Adaptive Particle Swarm Optimization Long Short-Term Memory (CAPSO-LSTM) model, utilizing a comprehensive dataset from Beijing (1998-2021) to train and test the model. The CAPSO-LSTM model, which integrates a cosine adaptive mechanism into particle swarm optimization, advances the optimization of long short-term memory (LSTM) network hyperparameters. Comparative analyses are conducted against conventional LSTM and Partical Swarm Optimization (PSO)-LSTM frameworks, employing mean absolute error (MAE), root mean square error (RMSE), and mean absolute percentage error (MAPE) as evaluative benchmarks. The findings indicate that the CAPSO-LSTM model exhibits a substantial improvement in prediction accuracy over the LSTM model, manifesting as a 66.33% decrease in MAE, a 73.78% decrease in RMSE, and a 57.14% decrease in MAPE. Similarly, when compared to the PSO-LSTM model, the CAPSO-LSTM model demonstrates a 58.36% decrease in MAE, a 65.39% decrease in RMSE, and a 50% decrease in MAPE. These results underscore the efficacy of the CAPSO-LSTM model in enhancing urban green space area prediction, suggesting its significant potential for aiding urban planning and environmental policy formulation.

11.
BMC Med ; 22(1): 252, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38886794

ABSTRACT

BACKGROUND: Previous studies have shown that the addition of platinum to neoadjuvant chemotherapy (NAC) improved outcomes for patients with triple-negative breast cancer (TNBC). However, no studies have assessed the efficacy and safety of the combination of taxane and lobaplatin. In this study, we conducted a randomized controlled phase II clinical study to compare the efficacy and safety of taxane combined with lobaplatin or anthracycline. METHODS: We randomly allocated patients with stage I-III TNBC into Arm A and Arm B. Arm A received six cycles of taxane combined with lobaplatin (TL). Arm B received six cycles of taxane combined with anthracycline and cyclophosphamide (TEC) or eight cycles of anthracycline combined with cyclophosphamide and sequential use of taxane (EC-T). Both Arms underwent surgery after NAC. The primary endpoint was the pathologic complete response (pCR). Secondary endpoints were event-free survival (EFS), overall survival (OS), and safety. RESULTS: A total of 103 patients (51 in Arm A and 52 in Arm B) were assessed. The pCR rate of Arm A was significantly higher than that of Arm B (41.2% vs. 21.2%, P = 0.028). Patients with positive lymph nodes and low neutrophil-to-lymphocyte ratio (NLR) benefited significantly more from Arm A than those with negative lymph nodes and high NLR (Pinteraction = 0.001, Pinteraction = 0.012, respectively). There was no significant difference in EFS (P = 0.895) or OS (P = 0.633) between the two arms. The prevalence of grade-3/4 anemia was higher in Arm A (P = 0.015), and the prevalence of grade-3/4 neutropenia was higher in Arm B (P = 0.044). CONCLUSIONS: Neoadjuvant taxane plus lobaplatin has shown better efficacy than taxane plus anthracycline, and both regimens have similar toxicity profiles. This trial may provide a reference for a better combination strategy of immunotherapy in NAC for TNBC in the future.


Subject(s)
Anthracyclines , Antineoplastic Combined Chemotherapy Protocols , Cyclobutanes , Neoadjuvant Therapy , Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/drug therapy , Female , Middle Aged , Neoadjuvant Therapy/methods , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cyclobutanes/administration & dosage , Cyclobutanes/therapeutic use , Anthracyclines/therapeutic use , Anthracyclines/administration & dosage , Aged , Taxoids/therapeutic use , Taxoids/administration & dosage , Organoplatinum Compounds/therapeutic use , Organoplatinum Compounds/administration & dosage , Treatment Outcome , Cyclophosphamide/administration & dosage , Cyclophosphamide/therapeutic use , Bridged-Ring Compounds
12.
Int J Clin Oncol ; 2024 Jun 09.
Article in English | MEDLINE | ID: mdl-38853186

ABSTRACT

BACKGROUND: The late-stage diagnosis and distant metastasis of oral squamous cell carcinoma (OSCC) remain a huge challenge to clinical treatment for OSCC. During the past decades, targeting glycolysis-inducing factors becomes an attractive new strategy in OSCC therapies. METHODS: OSCC cells were stimulated with hypoxia or transfected with agomir-199a-5p, antagomir-199a-5p, and siRNA for HIF1A, cell proliferation was detected by CCK-8 assay; HIF1α, GLUT1, HK2 and LDHA expression levels were examined with western blot; miR-199 expression was determined with RT-PCR; cell migratory and invasive abilities were examined using wound healing and transwell assays; the lactate and glucose in culture medium were also determined. Luciferase assay or CHIP assay was applied for confirm the binding between miR-199a-5p and HIF1A 3'UTR, or between HIF1α and miR-199a promoter. RESULTS: HIF1α showed to be abnormally up-regulated, and miR-199a-5p showed to be abnormally down-regulated within OSCC under hypoxia. Hypoxia considerably enhanced OSCC cell proliferation, glycolysis, migratory ability, and invasive ability. MiR-199a-5p bound to HIF1A 3'-UTR and suppressed HIF1A expression; HIF1α targeted miR-199a-5p promoter region and downregulated miR-199a-5p expression. Under hypoxia, miR-199a-5p overexpression significantly repressed HIF1α up-regulation inresponse to hypoxia, OSCC cell proliferation, glycolysis, migratory ability, and invasive ability. CONCLUSION: miR-199a-5p and HIF1α form a dual-regulatory axis in OSCC cells; the miR-199a-5p/HIF1α dual-regulatory axis contributes to hypoxia-induced aggressive OSCC phenotypes.

13.
J Am Chem Soc ; 146(25): 17170-17179, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38865584

ABSTRACT

Selective activation of C-H bonds in light alkanes under mild conditions is challenging but holds the promise of efficient upgrading of abundant hydrocarbons. In this work, we report the conversion of propane to propylene with ∼95% selectivity on Cu(I)-ZSM-5 with O2 at room temperature and pressure. The intraporous Cu(I) species was oxidized to Cu(II) during the reaction but could be regenerated with H2 at 220 °C. Diffuse reflectance ultraviolet spectroscopy indicated the presence of both Cu+-O2 and Cu2(µ-O2)2+ species in the zeolite pores during the reaction, and electron paramagnetic resonance results showed that propane activation occurred via a radical-mediated pathway distinct from that with H2O2 as the oxidant. Correlation between spectroscopic and reactivity results on Cu(I)-ZSM-5 with different Cu loadings suggests that the isolated intraporous Cu(I) species is the main active species in propane activation.

14.
J Chem Theory Comput ; 20(12): 5317-5336, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38865109

ABSTRACT

Despite the success of AlphaFold methods in predicting single protein structures, these methods showed intrinsic limitations in the characterization of multiple functional conformations of allosteric proteins. The recent NMR-based structural determination of the unbound ABL kinase in the active state and discovery of the inactive low-populated functional conformations that are unique for ABL kinase present an ideal challenge for the AlphaFold2 approaches. In the current study, we employ several adaptations of the AlphaFold2 methodology to predict protein conformational ensembles and allosteric states of the ABL kinase including randomized alanine sequence scanning combined with the multiple sequence alignment subsampling proposed in this study. We show that the proposed new AlphaFold2 adaptation combined with local frustration profiling of conformational states enables accurate prediction of the protein kinase structures and conformational ensembles, also offering a robust approach for interpretable characterization of the AlphaFold2 predictions and detection of hidden allosteric states. We found that the large high frustration residue clusters are uniquely characteristic of the low-populated, fully inactive ABL form and can define energetically frustrated cracking sites of conformational transitions, presenting difficult targets for AlphaFold2. The results of this study uncovered previously unappreciated fundamental connections between local frustration profiles of the functional allosteric states and the ability of AlphaFold2 methods to predict protein structural ensembles of the active and inactive states. This study showed that integration of the randomized sequence scanning adaptation of AlphaFold2 with a robust landscape-based analysis allows for interpretable atomistic predictions and characterization of protein conformational ensembles, providing a physical basis for the successes and limitations of current AlphaFold2 methods in detecting functional allosteric states that play a significant role in protein kinase regulation.


Subject(s)
Protein Conformation , Proto-Oncogene Proteins c-abl , Proto-Oncogene Proteins c-abl/chemistry , Proto-Oncogene Proteins c-abl/metabolism , Allosteric Regulation , Humans , Models, Molecular , Amino Acid Sequence
15.
ACS Appl Mater Interfaces ; 16(26): 34069-34078, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38898563

ABSTRACT

Polyether-based polymer electrolytes are attractive but still challenging for high-energy-density solid-state lithium metal batteries due to their limited Li-ion conductivity at room temperature. Herein, an oligomeric polyethylene glycol methyl ether methacrylate (PEGMEM)-modified silica-coated polyimide fibrous scaffold (PINF@PEGMEM-SiO2) was introduced in polyethylene glycol dimethyl ether (PEGDME) to enhance the Li-ion transportation at room temperature. PINF@PEGMEM-SiO2 was developed to build a continuous and interconnected interface for continuous Li-ion transportation in bulk. The carbonyl groups (C═O) of PEGMEM on SiO2 can promote the dissociation of lithium salts and enhance the migration of free Li ions at the interface. The same -C-C-O- unit contained in both PEGMEM and PEGDME ensures the compatibility of PEGMEM at the interface and PEGDME in the bulk. The prepared PEGDME-based polymer electrolyte exhibits a high ionic conductivity of 1.14 × 10-4 S cm-1 at 25 °C and an improved Li-ion transference number of 0.41. Furthermore, LiFePO4/Li and LiNi0.8Co0.1Mn0.1O2/Li cells with excellent cyclability and rate capability at ambient temperature are obtained.

16.
Front Bioeng Biotechnol ; 12: 1426477, 2024.
Article in English | MEDLINE | ID: mdl-38915336

ABSTRACT

Background: Branched gold and silver nanoparticles coated with polydopamine (Au-Ag-PDA) demonstrate high photothermal conversion efficiency. Utilizing umbilical cord mesenchymal stem cell membranes (MSCM) as an effective drug delivery system, our preliminary studies investigated the suppression of sebum secretion in sebaceous glands using MSCM-coated Au-Ag-PDA nano-particles (Au-Ag-PDA@MSCM) combined with 808 nm laser irradiation, showing potential for dermatological applications in acne treatment. Methods: This study employs proteomic analysis, complemented by subsequent techniques such as Western blotting (WB), small interfering RNA (siRNA), and transmission electron microscopy, to further investigate the differential mechanisms by which Au-Ag-PDA and Au-Ag-PDA@MSCM-mediated photothermal therapy (PTT) suppress sebum secretion. Results: Our proteomic analysis indicated mitochondrial respiratory chain damage in sebaceous gland tissues post-PTT, with further validation revealing ferroptosis in sebaceous cells and tissues. Acyl-CoA Synthetase Long-Chain Family Member 4 (Acsl4) has been identified as a critical target, with Au-Ag-PDA@MSCM demonstrating enhanced ferroptotic effects. Conclusion: These findings significantly advance our understanding of how PTT mediated by Au-Ag-PDA@MSCM nanoparticles reduces sebum secretion and underscore the pivotal role of MSCM in inducing ferroptosis in sebaceous glands, thus providing a robust theoretical foundation for employing PTT via specific molecular pathways in acne treatment.

17.
Cell Discov ; 10(1): 63, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38862482

ABSTRACT

Conjunctival melanoma (CoM) is a potentially devastating tumor that can lead to distant metastasis. Despite various therapeutic strategies for distant metastatic CoM, the clinical outcomes remain unfavorable. Herein, we performed single-cell RNA sequencing (scRNA-seq) of 47,017 cells obtained from normal conjunctival samples (n = 3) and conjunctival melanomas (n = 7). Notably, we noticed a higher abundance of cancer-associated fibroblasts (CAFs) in tumor microenvironment (TME), correlated with enhanced angiogenic capacity and increased VEGFR expression in distal metastatic CoM. Additionally, we observed a significant decrease in the proportion of total CD8+ T cells and an increase in the proportion of naive CD8+ T cells, contributing to a relatively quiescent immunological environment in distal metastatic CoM. These findings were confirmed through the analyses of 70,303 single-cell transcriptomes of 7 individual CoM samples, as well as spatially resolved proteomes of an additional 10 samples of CoMs. Due to the increase of VEGFR-mediated angiogenesis and a less active T cell environment in distal metastatic CoMs, a clinical trial (ChiCTR2100045061) has been initiated to evaluate the efficacy of VEGFR blockade in combination with anti-PD1 therapy for patients with distant metastatic CoM, showing promising tumor-inhibitory effects. In conclusion, our study uncovered the landscape and heterogeneity of the TME during CoM tumorigenesis and progression, empowering clinical decisions in the management of distal metastatic CoM. To our knowledge, this is the initial exploration to translate scRNA-seq analysis to a clinical trial dealing with cancer, providing a novel concept by accommodating scRNA-seq data in cancer therapy.

18.
Adv Sci (Weinh) ; : e2309940, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38874114

ABSTRACT

Liver fibrosis is a chronic pathological condition lacking specific clinical treatments. Stem cells, with notable potential in regenerative medicine, offer promise in treating liver fibrosis. However, stem cell therapy is hindered by potential immunological rejection, carcinogenesis risk, efficacy variation, and high cost. Stem cell secretome-based cell-free therapy offers potential solutions to address these challenges, but it is limited by low delivery efficiency and rapid clearance. Herein, an innovative approach for in situ implantation of smart microneedle (MN) arrays enabling precisely controlled delivery of multiple therapeutic agents directly into fibrotic liver tissues is developed. By integrating cell-free and platinum-based nanocatalytic combination therapy, the MN arrays can deactivate hepatic stellate cells. Moreover, they promote excessive extracellular matrix degradation by more than 75%, approaching normal levels. Additionally, the smart MN arrays can provide hepatocyte protection while reducing inflammation levels by ≈70-90%. They can also exhibit remarkable capability in scavenging almost 100% of reactive oxygen species and alleviating hypoxia. Ultimately, this treatment strategy can effectively restrain fibrosis progression. The comprehensive in vitro and in vivo experiments, supplemented by proteome and transcriptome analyses, substantiate the effectiveness of the approach in treating liver fibrosis, holding immense promise for clinical applications.

19.
Ann Plast Surg ; 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38896857

ABSTRACT

BACKGROUND: An increasing number of surgical and nonsurgical interventions are available in the field of female genital plastic surgery. The rate of female genital plastic surgery has increased by nearly 220 percent over the past 5 years. Despite several studies on the topic, no relevant bibliometric analysis has been conducted. METHODS: We searched the Web of Science Core Collection for articles related to female genital plastic surgery. CiteSpace 6.1.R2 (Drexel University, USA) and VOSviewer 1.6.10.0 (Leiden University, the Netherlands) were used, and national distribution, institutions, journals, authors, and key words were analyzed and calculated. RESULTS: From 2003 to 2022, 1299 papers in the field of female genital plastic surgery were retrieved. There were more articles produced in the United States, and there were also two institutions in the Netherlands that were highly productive. A wide and close relationship has been established between researchers and institutions conducting female genital plastic surgery. Professor Bouman MB published the most articles on female genital plastic surgery in the Journal of Sexual Medicine. Female genital plastic surgery dominated the top 10 references with the highest local citation score. There were four clusters of key words with the most citations, and the most recently trending key words were "vaginal agenesis," "transgender," and "congenital adrenal hyperplasia." CONCLUSIONS: The purpose of this article is to provide a summary of the current research status focusing on female genital plastic surgery. It is hoped that more efforts will be made to promote the development of female genital plastic surgery in the future.

20.
Imeta ; 3(3): e199, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38898986

ABSTRACT

The drug response phenotype is determined by a combination of genetic and environmental factors. The high clinical conversion failure rate of gene-targeted drugs might be attributed to the lack of emphasis on environmental factors and the inherent individual variability in drug response (IVDR). Current evidence suggests that environmental variables, rather than the disease itself, are the primary determinants of both gut microbiota composition and drug metabolism. Additionally, individual differences in gut microbiota create a unique metabolic environment that influences the in vivo processes underlying drug absorption, distribution, metabolism, and excretion (ADME). Here, we discuss how gut microbiota, shaped by both genetic and environmental factors, affects the host's ADME microenvironment within a new evaluation system for drug-microbiota interactions. Furthermore, we propose a new top-down research approach to investigate the intricate nature of drug-microbiota interactions in vivo. This approach utilizes germ-free animal models, providing foundation for the development of a new evaluation system for drug-microbiota interactions.

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