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1.
Article in English | MEDLINE | ID: mdl-38906273

ABSTRACT

BACKGROUND: Endolysosomal compartments are acidic and contain low pH-dependent proteases, and these conditions are exploited by respiratory viruses, such as SARS-CoV-2 and influenza virus, for escaping into the cytosol. Moreover, endolysosomes contain various pattern recognition receptors (PRRs), which respond to virus-derived pathogen-associated molecular patterns (PAMPs) by production of pro-inflammatory cytokines/chemokines. However, excessive pro-inflammatory responses can lead to a potentially lethal cytokine storm. OBJECTIVES: Here we investigated the endosomal PRR expression profile in primary human small airway epithelial cells (HSAECs), and whether blockade of endolysosomal acidification affects their cytokine/chemokine production after challenge with virus-derived stimulants. METHODS: HSAECs were exposed to stimulants mimicking virus-derived PAMPs, either in the absence or presence of compounds causing blockade of endolysosomal acidification, followed by measurement of cytokine expression and release. RESULTS: We show that toll-like receptor 3 (TLR3) is the major endosomal PRR expressed by HSAECs, and that TLR3 expression is strongly induced by TLR3 agonists, but not by a range of other PRR agonists. We also demonstrate that TLR3 engagement with its agonists elicits a robust pro-inflammatory cytokine/chemokine response, which is profoundly suppressed through blockade of endolysosomal acidification, by bafilomycin A1, monensin, or niclosamide. Using TLR3 reporter cells, it was confirmed that TLR3 signaling is strongly induced by Poly(I:C) and that blockade of endolysosomal acidification efficiently blocked TLR3 signaling. Finally, we show that blockade of endolysosomal acidification causes a reduction in the levels of TLR3 mRNA and protein. CONCLUSION: These findings show that blockade of endolysosomal acidification suppresses TLR3-dependent cytokine and chemokine production in HSAECs. CLINICAL IMPLICATION: These findings may be exploited for therapeutic strategies aiming to ameliorate the cytokine storm in response to respiratory virus infection.

2.
Arch Biochem Biophys ; 758: 110064, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38897534

ABSTRACT

Chemoresistance is one of the major hindrances to many cancer therapies, including esophageal squamous cell carcinoma (ESCC). Ferroptosis, a new programmed cell death, plays an essential role in chemoresistance. IQ-domain GTPase activating protein 1 (IQGAP1) is a scaffold protein and functions as an oncogene in various human malignancies. However, the underlying effect and molecular mechanisms of IQGAP1 on paclitaxel (PTX) resistance and ferroptosis in ESCC remain to be elucidated. In this study, we found that IQGAP1 was highly expressed in ESCC tissues and could as a potential biomarker for diagnosis and predicting the prognosis of ESCC. Functional studies revealed that IQGAP1 overexpression reduced the sensitivity of ESCC cells to PTX by enhancing ESCC cell viability and proliferation and inhibiting cell death, and protected ESCC cells from ferroptosis, whereas IQGAP1 knockdown exhibited contrary effects. Importantly, reductions of chemosensitivity and ferroptosis caused by IQGAP1 overexpression were reversed with ferroptosis inducer RSL3, while the increases of chemosensitivity and ferroptosis caused by IQGAP1 knockdown were reversed with ferroptosis inhibitor ferrostatin-1 (Fer-1) in ESCC cells, indicating that IQGAP1 played a key role in resistance to PTX through regulating ferroptosis. Mechanistically, we demonstrated that IQGAP1 overexpression upregulated the expression of Yes-associated protein (YAP), the central mediator of the Hippo pathway. YAP inhibitor Verteporfin (VP) could reverse the effects of IQGAP1 overexpression on ESCC chemoresistance and ferroptosis. Taken together, our findings suggest that IQGAP1 promotes chemoresistance by blocking ferroptosis through targeting YAP. IQGAP1 may be a novel therapeutic target for overcoming chemoresistance in ESCC.

3.
Aging Dis ; 2024 May 15.
Article in English | MEDLINE | ID: mdl-38916727

ABSTRACT

Endogenous retroviruses (ERVs), a subset of genomic transposable elements (TEs) in a broader sense, have remained latent within mammalian genomes for tens of millions of years. These genetic elements are typically in a silenced state due to stringent regulatory mechanisms. However, under specific conditions, they can become activated, triggering inflammatory responses through diverse mechanisms. This activation has been shown to play a potential role in various neurological disorders, tumors, and cellular senescence. Consequently, the regulation of ERV expression through various methods holds promise for clinical applications in disease treatment. ERVs also engage in interactions with a variety of exogenous viruses, thereby influencing the outcomes of viral infectious diseases. This article comprehensively reviews the pathogenic cascade of ERVs, encompassing activation, inflammation, associated diseases, senescence, and interplay with viruses. Additionally, it outlines therapeutic strategies targeting ERVs with the aim of offering novel research directions for understanding the relationship between ERVs and diseases, along with corresponding treatment modalities.

4.
Bioorg Chem ; 148: 107450, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38761704

ABSTRACT

Here, a series of 3-(6-aminopyridin-3-yl) benzamide derivatives were designed and synthesized. Cell viability assay indicated that most compounds exhibited potent antiproliferative activity against all the tested cancer cells. Among them, compound 7l displayed the best antiproliferative activity particularly in A549 cells, with an IC50 value of 0.04 ± 0.01 µM. RNA-seq analysis was employed to explore the potential pathways related to the antiproliferative activity of compound 7l. The data revealed that 7l exerted antiproliferative activity mainly by regulating cell cycle, DNA replication and p53 signaling pathway. Indeed, compound 7l induced G2/M phase arrest by AURKB transcription inhibition and resulted in cell apoptosis via p53 signaling pathway. Most importantly, compound 7l demonstrated potent antitumor activity in A549 xenograft tumor model. Collectively, 7l might be a promising lead compound for the development of new therapeutic agents for AURKB overexpressed or mutated cancers.


Subject(s)
Antineoplastic Agents , Apoptosis , Benzamides , Cell Cycle Checkpoints , Cell Proliferation , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Benzamides/pharmacology , Benzamides/chemical synthesis , Benzamides/chemistry , Cell Proliferation/drug effects , Structure-Activity Relationship , Molecular Structure , Cell Cycle Checkpoints/drug effects , Animals , Mice , Mice, Nude , Cell Line, Tumor , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Transcription, Genetic/drug effects , Mice, Inbred BALB C
5.
Nat Commun ; 15(1): 4122, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38750027

ABSTRACT

Visual information is important for accurate spatial coding and memory-guided navigation. As a crucial area for spatial cognition, the medial entorhinal cortex (MEC) harbors diverse spatially tuned cells and functions as the major gateway relaying sensory inputs to the hippocampus containing place cells. However, how visual information enters the MEC has not been fully understood. Here, we identify a pathway originating in the secondary visual cortex (V2) and directly targeting MEC layer 5a (L5a). L5a neurons served as a network hub for visual processing in the MEC by routing visual inputs from multiple V2 areas to other local neurons and hippocampal CA1. Interrupting this pathway severely impaired visual stimulus-evoked neural activity in the MEC and performance of mice in navigation tasks. These observations reveal a visual cortical-entorhinal pathway highlighting the role of MEC L5a in sensory information transmission, a function typically attributed to MEC superficial layers before.


Subject(s)
Entorhinal Cortex , Neurons , Spatial Navigation , Visual Cortex , Animals , Entorhinal Cortex/physiology , Visual Cortex/physiology , Spatial Navigation/physiology , Mice , Neurons/physiology , Male , Mice, Inbred C57BL , Photic Stimulation , CA1 Region, Hippocampal/physiology , CA1 Region, Hippocampal/cytology , Visual Pathways/physiology , Visual Perception/physiology
6.
Cancer Lett ; 589: 216833, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38548217

ABSTRACT

Understanding the intrinsic mechanisms underpinning cancer metabolism and therapeutic resistance is of central importance for effective nutrition-starvation therapies. Here, we report that Interleukin 1A (IL1A) mRNA and IL-1α protein facilitate glutathione (GSH) synthesis to counteract oxidative stress and resistance against nutrition-starvation therapy in oral squamous cell carcinoma (OSCC). The expression of IL1A mRNA was elevated in the case of OSCC associated with unfavorable clinical outcomes. Both IL1A mRNA and IL-1α protein expression were increased under glucose-deprivation in vitro and in vivo. The transcription of IL1A mRNA was regulated in an NRF2-dependent manner in OSCC cell lines under glucose-deprivation. Moreover, the IL-1α conferred resistance to oxidative stress via GSH synthesis in OSCC cell lines. The intratumoral administration of siRNAs against IL1A mRNA markedly reversed GSH production and sensitized OSCC cells to Anlotinib in HN6 xenograft models. Overall, the current study demonstrates novel evidence that the autocrine IL-1α favors endogenous anti-oxidative process and confers therapeutic resistance to nutrition-starvation in OSCCs.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Mouth Neoplasms/pathology , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/metabolism , Squamous Cell Carcinoma of Head and Neck , Oxidative Stress , Glutathione/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Cell Line, Tumor
8.
Brain Topogr ; 2024 Feb 19.
Article in English | MEDLINE | ID: mdl-38374489

ABSTRACT

Numerous studies utilizing magnetic resonance imaging (MRI) have observed sex and interhemispheric disparities in sulcal morphology, which could potentially underpin certain functional disparities in the human brain. Most of the existing research examines the precentral sulcus comprehensively, with a rare focus on its subsections. To explore the morphology, asymmetry, and sex disparities within the inferior precentral sulcus (IPCS), we acquired 3.0T magnetic resonance images from 92 right-handed Chinese adolescents. Brainvisa was used to reconstruct the IPCS structure and calculate its mean depth (MD). Based on the morphological patterns of IPCS, it was categorized into five distinct types. Additionally, we analyzed four different types of spatial relationships between IPCS and inferior frontal sulcus (IFS). There was a statistically significant sex disparity in the MD of IPCS, primarily observed in the right hemisphere. Females exhibited significantly greater asymmetry in the MD of IPCS compared to males. No statistically significant sex or hemispheric variations were identified in sulcal patterns. Our findings expand the comprehension of inconsistencies in sulcal structure, while also delivering an anatomical foundation for the study of related regions' function.

9.
Adv Wound Care (New Rochelle) ; 13(6): 322-328, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38258794

ABSTRACT

Objective: This study is the first prospective within-patient self-controlled research seeking to investigate the safety and efficacy of 595 nm pulsed-dye laser (PDL) for the treatment of cleft-lip scars. Approach: This prospective, randomized, self-controlled study is based on the clinical records of the patients who received laser-assisted treatment due to bilateral cleft-lip scars. The bilateral scars were randomly assigned to the 595 nm PDL group with five consecutive sessions at 2-week intervals or control group in a blinded manner of evaluators, with subsequent follow-up for 6 months after the final treatment. Clinical efficacy and safety outcomes were evaluated by Vancouver Scar Scale (VSS), Patient Scar Assessment Questionnaire (PSAQ), and other objective evaluations. Results: A total of 18 patients were included. The 595 nm PDL-treated sides showed statistically significant improvement in VSS after treatment at follow-up compared with the baseline (p < 0.05). Interestingly, the 595 nm-PDL-treated side achieved significantly better improvement in scar pigmentation and pliability (p < 0.05). Though there was statistically significant difference between two groups (p < 0.05), the gap in overall PSAQ is not obvious. And comparison by area and coloring evaluation (E/M index) also suggests that the responses of scars to treatment by PDL were slightly improved (p < 0.05). Innovation and Conclusion: It is the first time to apply the 595nm PDL for cleft-lip scars. It would be a better choice for the early treatment of red scar with proliferative tendency after cleft-lip surgery.


Subject(s)
Cicatrix , Cleft Lip , Lasers, Dye , Humans , Female , Male , Lasers, Dye/therapeutic use , Prospective Studies , Treatment Outcome , Cleft Lip/surgery , Cleft Lip/complications , Asian People , Adult , Adolescent , Child , Low-Level Light Therapy/methods , Young Adult
10.
Biochem Cell Biol ; 102(2): 169-178, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-37917979

ABSTRACT

Esophageal squamous cell carcinoma (ESCC) is a common malignancy with high morbidity and mortality. Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) serves as a reader of RNA m6A (N6 methyladenosine) modification to regulate gene expression at the post-transcriptional level. Emerging evidence suggests that IGF2BP2 plays critical roles in tumorigenesis and malignant development. However, the biological function and molecular mechanism of IGF2BP2 in ESCC are not well understood. Here, we found that IGF2BP2 expression was upregulated in esophageal cancer tissues and ESCC cells, and IGF2BP2 overexpression enhanced proliferation, migration, invasion, and stem cell-like properties of ESCC cells. Conversely, the knockdown of IGF2BP2 expression inhibited malignant phenotype of ESCC cells. Mechanistically, IGF2BP2 upregulated octomer-binding transcription factor 4 (OCT4) mRNA expression, and RNA immunoprecipitation (RIP) assay proved that IGF2BP2 could interact with OCT4 mRNA. Moreover, OCT4 was modified at m6A confirmed by methylated m6A RNA immunoprecipitation (Me-RIP)-qPCR assay, and IGF2BP2 knockdown reduced OCT4 mRNA stability. These results suggested that IGF2BP2 served as a reader for m6A-modified OCT4, thus increased OCT4 mRNA expression by regulating its stability. Furthermore, the knockdown of OCT4 could reverse the effects of IGF2BP2 on ESCC cells. In conclusion, these data indicate that IGF2BP2, as a reader for m6A, plays an oncogenic role by regulating OCT4 expression in ESCC, which provides new insights into targeting IGF2BP2/OCT4 axis for the therapy of ESCC.


Subject(s)
Adenine/analogs & derivatives , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , RNA, Messenger/genetics , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Neoplasms/genetics , RNA , Cell Proliferation , Cell Line, Tumor , RNA-Binding Proteins/genetics
11.
J Colloid Interface Sci ; 658: 678-687, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38134676

ABSTRACT

Organic compounds have become an important electrode material for aqueous electrochemical energy storage. However, organic electrodes still face poor performance in aqueous batteries due to insufficient electrochemical activity. In this work, a novel conjugated quinone compound containing a rich carbonyl group was designed. The quinone compound was synthesized by a simple dehydration reaction of pyrene-4,5,9,10-tetrone (PTO) and 1,2-diaminoanthraquinone (1,2-AQ); it contains 4 pyrazines (CN) from AQ and 4 carbonyl groups (CO), as well as a large number of active sites and the excellent conductivity brought by its conjugated structure ensures the high theoretical capacity of PTO-AQ. In the context of aqueous sodium ion batteries (ASIBs), the electrode material known as PTO-AQ exhibits a notable reversible discharge capacity of 117.9 mAh/g when subjected to a current density of 1 A/g; impressively, it maintained a capacity retention rate of 74.3 % even after undergoing 500 charge and discharge cycles, a performance significantly surpassing that of pristine PTO and AQ. Notably, PTO-AQ exhibits a wide operating voltage range (-1.0-0.5 V) and a cycle life of up to 10,000 cycles. In situ Raman and ex situ measurements were used to analyze the structural changes of PTO-AQ during charge and discharge and the energy storage mechanism in NaAC. The effective promotion of Na+ storage brought by a rich carbonyl group was obtained. The structural energy level and electrostatic potential of PTO-AQ were calculated, and the active center distribution of PTO-AQ was obtained. This work serves as a guide for designing high-performance aqueous organic electrode materials that operate across a wide voltage range while also explaining their energy storage mechanism.

12.
Mol Biotechnol ; 2023 Sep 26.
Article in English | MEDLINE | ID: mdl-37751128

ABSTRACT

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors. Ferroptosis is a new form of regulated cell death and targeting ferroptosis provides a novel therapeutic approach for human cancers. Verteporfin (VP) has been identified as a Yes-associated protein (YAP) inhibitor for treatment of several human cancers. However, it remains unclear whether VP exerts anticancer activity by inducing ferroptosis in ESCC cells. In the current study, we found that VP reduced cell viability and led to cell death in ESCC cell lines (KYSE150 and KYSE30) by inhibiting YAP expression. Subsequently, the findings revealed that VP treatment triggered significant ferroptosis events, including accumulation of Fe2+, reactive oxygen species (ROS) and malondialdehyde (MDA), reduction of mitochondrial membrane potential (MMP), glutathione (GSH) and glutathione peroxidase 4 (GPX4) expression. Further study showed that the effects of ESCC cell proliferation and death caused by VP could be reversed by ferroptosis inhibitor ferrostatin-1 (Fer-1). Moreover, VP enhanced the chemosensitivity of ESCC resistant cells to paclitaxel (PTX). And VP combined with PTX can synergistically inhibit cell proliferation and induce cell death by triggering ferroptosis of PTX-resistant cells. All these data suggested that VP suppressed ESCC cell survival and reversed resistance to PTX through inducing ferroptosis, which may provide a promising therapeutic strategy for ESCC.

13.
Cell Rep ; 42(7): 112782, 2023 07 25.
Article in English | MEDLINE | ID: mdl-37436894

ABSTRACT

Layer 1 (L1) interneurons (INs) participate in various brain functions by gating information flow in the neocortex, but their role in the medial entorhinal cortex (MEC) is still unknown, largely due to scant knowledge of MEC L1 microcircuitry. Using simultaneous triple-octuple whole-cell recordings and morphological reconstructions, we comprehensively depict L1IN networks in the MEC. We identify three morphologically distinct types of L1INs with characteristic electrophysiological properties. We dissect intra- and inter-laminar cell-type-specific microcircuits of L1INs, showing connectivity patterns different from those in the neocortex. Remarkably, motif analysis reveals transitive and clustered features of L1 networks, as well as over-represented trans-laminar motifs. Finally, we demonstrate the dorsoventral gradient of L1IN microcircuits, with dorsal L1 neurogliaform cells receiving fewer intra-laminar inputs but exerting more inhibition on L2 principal neurons. These results thus present a more comprehensive picture of L1IN microcircuitry, which is indispensable for deciphering the function of L1INs in the MEC.


Subject(s)
Entorhinal Cortex , Neocortex , Entorhinal Cortex/physiology , Interneurons/physiology , Neurons/physiology , Electrophysiological Phenomena
14.
Int J Biol Macromol ; 248: 125726, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37422249

ABSTRACT

The extraction process, structural characterization and free radical scavenging ability of polysaccharides from Camellia oleifera have already been widely studied. However, the antioxidant activities are still lack of systematic experiments. In this study, we used Hep G2 cells and Caenorhabditis elegans to evaluate the antioxidant potential of polysaccharides that from C. oleifera flowers (P-CF), leaves (P-CL), seed cakes (P-CC) and fruit shells (P-CS). The results showed all these polysaccharides could protect cells from oxidative damage induced by t-BHP. The highest cell viabilities were 66.46 ± 1.36 % (P-CF), 55.2 ± 2.93 % (P-CL), 54.49 ± 1.29 % (P-CC) and 61.45 ± 1.67 % (P-CS), respectively. Studies have shown that four polysaccharides may protect cells from apoptosis by reducing ROS levels and maintaining MMP balance. Moreover, P-CF, P-CL, P-CC and P-CS increased the survival rate of C. elegans under thermal stress, which reduced the production of ROS by 56.1 ± 0.67 %, 59.37 ± 1.79 %, 16.63 ± 2.51 % and 27.55 ± 2.62 %, respectively. P-CF and P-CL showed stronger protective effects on C. elegans by increasing the nuclear entry rate of DAF-16 and stimulating the expression of SOD-3. Our study suggested that C. oleifera polysaccharides have the potential to develop into a natural supplement agent.


Subject(s)
Antioxidants , Camellia , Animals , Antioxidants/pharmacology , Antioxidants/chemistry , Reactive Oxygen Species/pharmacology , Caenorhabditis elegans , Camellia/chemistry , Polysaccharides/pharmacology , Polysaccharides/chemistry
15.
J Colloid Interface Sci ; 650(Pt B): 1811-1820, 2023 Nov 15.
Article in English | MEDLINE | ID: mdl-37506421

ABSTRACT

One of the biggest obstacles to the development of aqueous proton batteries (APBs), despite numerous optimization techniques, is the preparation and use of high-performance electrode materials. In this work, to improve the high solubility, limited capacity and poor cycle life of small organic molecules in APBs, homogeneous dispersed quinone-amine polymer nanospheres (PQANS) (average diameter: 220 nm) were synthesized by a polymerization reaction based on 3,3'-diaminobenzidine (DAB) and benzoquinone (BQ), making them suitable for proton storage in aqueous systems. As an anode for APBs, the obtained PQANS exhibits an improved reversible capacity of 126.2 mAh/g at 1 A/g after 300 cycles. The durable stable measurement of PQANS at 10 A/g was also conducted with a specific capacity of 66.8 mAh/g after 12,000 cycles. A series of in situ or ex situ measurements were used to establish the superior H+ storage mechanism of PQANS. A novel reaction mechanism of redox enhancement was revealed due to the existence of more carbonyl groups after the first cycle. Theoretical calculations were conducted to help illustrate the principle of binding protons with functional groups in PQANS. Finally, a PQANS anode-based aqueous proton full battery was constructed to demonstrate its potential application, which exhibits a specific capacity of 50.6 mAh/g at 1 A/g (600 cycles). This work provides a reference for preparing high-performance polymer-based electrode materials in aqueous batteries.

16.
Molecules ; 28(5)2023 Feb 23.
Article in English | MEDLINE | ID: mdl-36903353

ABSTRACT

Lithium-ion batteries (LIBs) have become the preferred battery system for portable electronic devices and transportation equipment due to their high specific energy, good cycling performance, low self-discharge, and absence of memory effect. However, excessively low ambient temperatures will seriously affect the performance of LIBs, which are almost incapable of discharging at -40~-60 °C. There are many factors affecting the low-temperature performance of LIBs, and one of the most important is the electrode material. Therefore, there is an urgent need to develop electrode materials or modify existing materials in order to obtain excellent low-temperature LIB performance. A carbon-based anode is one candidate for use in LIBs. In recent years, it has been found that the diffusion coefficient of lithium ion in graphite anodes decreases more obviously at low temperatures, which is an important factor limiting its low-temperature performance. However, the structure of amorphous carbon materials is complex; they have good ionic diffusion properties, and their grain size, specific surface area, layer spacing, structural defects, surface functional groups, and doping elements may have a greater impact on their low-temperature performance. In this work, the low-temperature performance of LIBs was achieved by modifying the carbon-based material from the perspectives of electronic modulation and structural engineering.

17.
J Cancer Res Clin Oncol ; 149(10): 7703-7716, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37000262

ABSTRACT

PURPOSE: Targeting angiogenesis is an attractive strategy for the effective treatment of cancer. This study aimed to investigate the anti-cancer activities of YAP inhibitor verteporfin (VP) in esophageal squamous cell carcinoma (ESCC) cells through its inhibitory effect on tumor angiogenesis. METHODS: Cell proliferation, apoptosis, migration and invasion abilities were estimated by MTT, colony formation, DAPI staining, wound healing and transwell assays, respectively. Human umbilical vein endothelial cell (HUVEC) tube formation assay and chick embryo chorioallantoic membrane (CAM) model were used to observe angiogenesis in vitro and in vivo. The interactions between ESCC cells and HUVECs were assessed by cell chemotactic migration and adhesion assays. The expression levels of angiogenesis-related molecules were detected by Western blot. RESULTS: We found that VP was potential to inhibit ESCC cell proliferation, migration, invasion and induce apoptosis in the dose-dependent fashion. VP also significantly suppressed proliferation, migration, and tube formation of HUVECs and promoted apoptosis of HUVECs, and reduced angiogenesis in CAM. Moreover, VP inhibited ESCC cell-induced angiogenesis in vitro by decreasing HUVEC chemotactic migration, adhesion and tube formation, and also reduced ESCC cell-induced neovascularization of the CAM in vivo. In addition, VP suppressed the expression of pro-angiogenic molecules such as VEGFA, MMP-2 and ß-catenin in ESCC cells. Furtherly, VP increased the chemosensitivity of ESCC-resistant cells to paclitaxel (PTX). The combination of VP and PTX attenuated the resistant cell-mediated angiogenesis in vitro and in vivo. CONCLUSION: These results reveal for the first time that VP potently inhibits malignant progression and overcomes chemoresistance of ESCC cells via inhibition of tumor angiogenesis. It provides insight into a new strategy for the treatment of ESCC that VP could be a potential drug candidate for targeting tumor angiogenesis.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Animals , Chick Embryo , Humans , Esophageal Squamous Cell Carcinoma/pathology , Verteporfin/pharmacology , Verteporfin/therapeutic use , Esophageal Neoplasms/pathology , Drug Resistance, Neoplasm , Neovascularization, Pathologic/pathology , Paclitaxel/pharmacology , Paclitaxel/therapeutic use , Cell Proliferation , Cell Line, Tumor , Cell Movement
18.
Biomater Sci ; 11(8): 2787-2808, 2023 Apr 11.
Article in English | MEDLINE | ID: mdl-36825722

ABSTRACT

The recent approvals for antibody-drug conjugates (ADCs) in multiple malignancies in the past few years have fueled the ongoing development of this class of drug. However, the limitation of ADCs is selectivity toward cancer cells especially overexpressing the antigen of interest. To broaden the anti-cancer spectrum of ADCs, combinatorial strategies of ADCs with chemotherapy have become a central focus of the current preclinical and clinical research. Here, we used the microtubule stabilizer paclitaxel and enfortumab vedotin-ejfv (EV), an ADC carrying the microtubule inhibitor payload monomethyl auristatin E (MMAE), for co-administration under the consideration of their mechanism of action associated with microtubules. We designed a sialic acid-cholesterol (SA-CH) conjugate-modified cationic liposome platform loaded with PTX (PTX-SAL) for efficiently targeting tumor-associated immune cells. Compared with monotherapy, PTX-SAL-mediated combination therapy with ADCs significantly inhibited S180 tumor growth in mice, with complete tumor regression occurring. The formation of a durable tumor-specific immunological memory response in mice that experienced complete tumor regression was assessed by secondary tumor cell rechallenge, and the production of memory T cells in the spleen was detected as related to the increased CD4+T memory cells and the enhanced serum IFN-γ. All our preliminary results throw light on the tremendous application potential for the application of this combination therapy regimen capable of mounting a durable immune response and stimulating a robust T cell-mediated tumor-specific immunological memory.


Subject(s)
Immunoconjugates , Paclitaxel , Mice , Animals , Liposomes , N-Acetylneuraminic Acid , Immunologic Memory , Cell Line, Tumor
19.
Dermatol Surg ; 49(2): 145-148, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36689573

ABSTRACT

OBJECTIVE: To determine the optimal time to apply a fractional CO 2 laser for the treatment of postsecondary repair scars in patients with cleft lip. METHODS: Forty-two patients with linear scarring after cleft lip repair were recruited from November 2021 to October 2022. A single-blind, randomized, controlled cohort study was conducted to examine the impact of fractional CO 2 laser treatment compared with conventional conservative treatment. Thirty patients started laser treatment at 1 month ( n = 10), 3 months ( n = 10), and 6 months ( n = 10) postoperatively, and 12 patients were in the control group. Each patient was treated with high-energy low-density fractional CO 2 laser treatment 3 times at an interval of 1 month. The Vancouver Scar Scale (VSS) was used for scar evaluation to determine vascularity, pigmentation, pliability, and height. RESULTS: The VSS scores decreased significantly after laser treatment ( p < .05), with the most significant improvement in scars in the group that started treatment 1 month after the surgery. CONCLUSION: Early postoperative fractional CO 2 laser treatment of cleft lip scars is more effective than later treatment.


Subject(s)
Cleft Lip , Lasers, Gas , Humans , Cicatrix/etiology , Cicatrix/surgery , Cicatrix/pathology , Cleft Lip/surgery , Cohort Studies , Treatment Outcome , Single-Blind Method , Lasers, Gas/therapeutic use
20.
Sci Total Environ ; 858(Pt 2): 159943, 2023 Feb 01.
Article in English | MEDLINE | ID: mdl-36356750

ABSTRACT

This paper serves to enhance the current knowledge base of airborne microplastics which is significantly smaller than that of microplastics in marine, freshwater and terrestrial environments. It systematically presents the prevalence, sources, fate, risks and mitigations of airborne microplastics through the review of >140 scientific papers published mainly in the last 10 years. Unlike the extant review, it places an emphasis on the indoor microplastics, the risks of airborne microplastics on animals and plants and their mitigations. The outdoor microplastics are mostly generated by the wear and tear of tires, brake pads, waste incineration and industrial activities. They have been detected in many regions worldwide at concentrations ranging from 0.3 particles/m3 to 154,000 particles/L of air even in the Pyrenees Mountains and the Arctic. As for indoor microplastics, the reported concentrations range from 1 piece/m3 to 9900 pieces/m2/day, and are frequently higher than those of the outdoor microplastics. They come from the wear and tear of walls and ceilings, synthetic textiles and furniture finishings. Airborne microplastics could be suspended and resuspended, entrapped, settle under gravity as well as interact with chemicals, microorganisms and other microplastic particles. In the outdoors, they could also interact with sunlight and be carried by the wind over long distance. Airborne microplastics could adversely affect plants, animals and humans, leading to reduced photosynthetic rate, retarded growth, oxidative stress, inflammatory responses and increased cancer risks in humans. They could be mitigated indirectly through filters attached to air-conditioning system and directly through source reduction, regulation and biodegradable substitutes.


Subject(s)
Microplastics , Plastics , Animals , Humans , Environmental Monitoring , Fresh Water , Textiles
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