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1.
J Cancer Prev ; 29(2): 25-31, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38957590

ABSTRACT

The identification of therapeutic target genes that are functionally involved in stemness is crucial to effectively cure patients with metastatic carcinoma. We have previously reported that inhibition of ribosomal protein L9 (RPL9) expression suppresses the growth of colorectal cancer (CRC) cells by inactivating the inhibitor of DNA-binding 1 (ID-1) signaling axis, which is functionally associated with cancer cell survival. In addition to cell proliferation, ID-1 is also involved in the maintenance of cancer stemness. Thus, we aimed in this study to investigate whether the function of RPL9 could correlate with CRC stem cell-like properties. Here, we demonstrated that siRNA silencing of RPL9 reduced the invasiveness and migrative capabilities of HT29 and HCT116 parental cell populations and the capacity for sphere formation in the HT29 parental cell population. CD133+ cancer stem cells (CSCs) were then separated from CD133- cancer cells of the HT29 parental cell culture and treated with RPL9-specific siRNAs to verify the effects of RPL9 targeting on stemness. As a result, knockdown of RPL9 significantly suppressed the proliferative potential of CD133+ colorectal CSCs, accompanied by a reduction in CD133, ID-1, and p-IκBα levels. In line with these molecular alterations, targeting RPL9 inhibited the invasion, migration, and sphere-forming capacity of CD133+ HT29 CSCs. Taken together, these findings suggest that RPL9 promotes CRC stemness via ID-1 and that RPL9 could be a potential therapeutic target for both primary CRC treatment and the prevention of metastasis and/or recurrence.

2.
Sci Rep ; 14(1): 14737, 2024 06 26.
Article in English | MEDLINE | ID: mdl-38926445

ABSTRACT

Network analysis provides an innovative approach to examining symptom-to-symptom interactions in mental health, and adverse external conditions may change the network structures. This study compared the networks of common risk factors and mental health problems (loneliness, depressive symptoms, and anxiety symptoms) in community-dwelling older people before and during COVID-19. Older adults (aged ≥ 60) at risk for depression were recruited through non-governmental organizations. Loneliness, depressive symptoms and anxiety symptoms were measured using the three-item Loneliness Scale (UCLA-3), nine-item Patient Health Questionnaire (PHQ-9), and seven-item Generalized Anxiety Disorder Scale (GAD-7), respectively. Data from 2549 (before) and 3506 (during COVID-19) respondents were included using propensity score matching. Being restless (GAD-7-item5) was most central, indicated by Expected Influence, in both pre and during COVID-19 networks despite low severity (mean score). The network during COVID-19 had higher global strength and edge variability than the pre-pandemic network, suggesting easier symptom spread and potentially more complex symptom presentation. In addition, feeling isolated from others (UCLA-3-item3) had stronger connections with feeling worthless/guilty (PHQ-9-item6) and anticipatory anxiety (GAD-7-item7) during COVID-19 than before. These findings may enhance our knowledge of the symptom structure of common mental health problems and the impacts of the pandemic. Targeting central symptoms may offer novel preventive strategies for older people.


Subject(s)
Anxiety , COVID-19 , Depression , Independent Living , Loneliness , Humans , COVID-19/psychology , COVID-19/epidemiology , Aged , Loneliness/psychology , Male , Female , Depression/epidemiology , Depression/psychology , Independent Living/psychology , Anxiety/psychology , Anxiety/epidemiology , Aged, 80 and over , SARS-CoV-2/isolation & purification , Risk Factors , Middle Aged , Mental Health , Surveys and Questionnaires
4.
Mol Cell Biol ; 44(6): 245-258, 2024.
Article in English | MEDLINE | ID: mdl-38804232

ABSTRACT

Betaine-homocysteine S-methyltransferase (BHMT) is one of the most abundant proteins in the liver and regulates homocysteine metabolism. However, the molecular mechanisms underlying Bhmt transcription have not yet been elucidated. This study aimed to assess the molecular mechanisms underlying Bhmt transcription and the effect of BHMT deficiency on metabolic functions in the liver mediated by liver receptor homolog-1 (LRH-1). During fasting, both Bhmt and Lrh-1 expression increased in the liver of Lrh-1f/f mice; however, Bhmt expression was decreased in LRH-1 liver specific knockout mice. Promoter activity analysis confirmed that LRH-1 binds to a specific site in the Bhmt promoter region. LRH-1 deficiency was associated with elevated production of reactive oxygen species (ROS), lipid peroxidation, and mitochondrial stress in hepatocytes, contributing to hepatic triglyceride (TG) accumulation. In conclusion, this study suggests that the absence of an LRH-1-mediated decrease in Bhmt expression promotes TG accumulation by increasing ROS levels and inducing mitochondrial stress. Therefore, LRH-1 deficiency not only leads to excess ROS production and mitochondrial stress in hepatocytes, but also disrupts the methionine cycle. Understanding these regulatory pathways may pave the way for novel therapeutic interventions against metabolic disorders associated with hepatic lipid accumulation.


Subject(s)
Betaine-Homocysteine S-Methyltransferase , Hepatocytes , Liver , Methionine , Mice, Knockout , Reactive Oxygen Species , Receptors, Cytoplasmic and Nuclear , Triglycerides , Animals , Liver/metabolism , Mice , Reactive Oxygen Species/metabolism , Receptors, Cytoplasmic and Nuclear/metabolism , Receptors, Cytoplasmic and Nuclear/genetics , Betaine-Homocysteine S-Methyltransferase/metabolism , Betaine-Homocysteine S-Methyltransferase/genetics , Hepatocytes/metabolism , Methionine/metabolism , Triglycerides/metabolism , Promoter Regions, Genetic/genetics , Male , Mice, Inbred C57BL , Mitochondria/metabolism , Lipid Peroxidation
5.
Am J Physiol Gastrointest Liver Physiol ; 327(1): G57-G69, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38713616

ABSTRACT

Inflammatory bowel disease (IBD) encompasses several debilitating chronic gastrointestinal (GI) inflammatory disorders, including Crohn's disease and ulcerative colitis. In both conditions, mucosal inflammation is a key clinical presentation associated with altered serotonin (5-hydroxytryptamine or 5-HT) signaling. This altered 5-HT signaling is also found across various animal models of colitis. Of the 14 known receptor subtypes, 5-HT receptor type 7 (5-HT7) is one of the most recently discovered. We previously reported that blocking 5-HT signaling with either a selective 5-HT7 receptor antagonist (SB-269970) or genetic ablation alleviated intestinal inflammation in murine experimental models of colitis. Here, we developed novel antagonists, namely, MC-170073 and MC-230078, which target 5-HT7 receptors with high selectivity. We also investigated the in vivo efficacy of these antagonists in experimental colitis by using dextran sulfate sodium (DSS) and the transfer of CD4+CD45RBhigh T cells to induce intestinal inflammation. Inhibition of 5-HT7 receptor signaling with the antagonists, MC-170073 and MC-230078, ameliorated intestinal inflammation in both acute and chronic colitis models, which was accompanied by lower histopathological damage and diminished levels of proinflammatory cytokines compared with vehicle-treated controls. Together, the data reveal that the pharmacological inhibition of 5-HT7 receptors by these selective antagonists ameliorates the severity of colitis across various experimental models and may, in the future, serve as a potential treatment option for patients with IBD. In addition, these findings support that 5-HT7 is a viable therapeutic target for IBD.NEW & NOTEWORTHY This study demonstrates that the novel highly selective 5-HT7 receptor antagonists, MC-170073 and MC-230078, significantly alleviated the severity of colitis across models of experimental colitis. These findings suggest that inhibition of 5-HT7 receptor signaling by these new antagonists may serve as an alternative mode of treatment to diminish symptomology in those with inflammatory bowel disease.


Subject(s)
Colitis , Receptors, Serotonin , Serotonin Antagonists , Animals , Receptors, Serotonin/metabolism , Receptors, Serotonin/drug effects , Colitis/drug therapy , Colitis/immunology , Colitis/pathology , Mice , Serotonin Antagonists/pharmacology , Mice, Inbred C57BL , Disease Models, Animal , Dextran Sulfate , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Intestinal Mucosa/immunology , Signal Transduction/drug effects , Severity of Illness Index , Colon/drug effects , Colon/pathology , Colon/metabolism , Colon/immunology , Male
6.
Sci Rep ; 14(1): 12458, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816437

ABSTRACT

In this study, we experimentally identify the effect of liquid dielectrophoresis (LDEP) force on a superhydrophobic surface in directing the trajectory of moving water droplets across designed interdigitated electrodes and show that this method is capable of rapidly selecting droplets at a high speed (200 mm/s). As the droplets traverse down the surface by the electric field, their deflection on the edge of these electrodes is achieved successively, allowing for the selective manipulation of discrete droplets. A series of experiments were conducted to validate the relationships among droplet deflections, applied electric fields, and dynamic contact angles. Our findings reveal that the principal driving force behind the droplet deflections is the LDEP force, which can provide instant manipulation of moving droplets rather than a variation in contact angles brought about by electrowetting. This study presents a proof-of-concept experiment utilizing LDEP for high-throughput droplet selection and also highlights the potential applications of this mechanism in high-speed digital microfluidics (DMF) and biological separation methodologies.

7.
Langmuir ; 40(22): 11548-11557, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38780514

ABSTRACT

Water incorporated with supramolecular building blocks in organic solvents can play a key role in the circularly polarized luminescence (CPL) inversion and amplification of supramolecular assemblies. Herein, we demonstrate that fine-tuning the water content regulated the assembly structure evolution and made the circular dichroism and CPL sign of the system undergo intriguing inversion, reinversion, and amplification processes based on a unique and interesting glutamide-cyanostilbene system, as supported by morphology, spectroscopic observations, and time-dependent density functional theory calculation.

8.
Commun Biol ; 7(1): 594, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38760406

ABSTRACT

Non-alcoholic fatty liver disease (NAFLD) is a chronic disease caused by hepatic steatosis. Adenosine deaminases acting on RNA (ADARs) catalyze adenosine to inosine RNA editing. However, the functional role of ADAR2 in NAFLD is unclear. ADAR2+/+/GluR-BR/R mice (wild type, WT) and ADAR2-/-/GluR-BR/R mice (ADAR2 KO) mice are fed with standard chow or high-fat diet (HFD) for 12 weeks. ADAR2 KO mice exhibit protection against HFD-induced glucose intolerance, insulin resistance, and dyslipidemia. Moreover, ADAR2 KO mice display reduced liver lipid droplets in concert with decreased hepatic TG content, improved hepatic insulin signaling, better pyruvate tolerance, and increased glycogen synthesis. Mechanistically, ADAR2 KO effectively mitigates excessive lipid production via AMPK/Sirt1 pathway. ADAR2 KO inhibits hepatic gluconeogenesis via the AMPK/CREB pathway and promotes glycogen synthesis by activating the AMPK/GSK3ß pathway. These results provide evidence that ADAR2 KO protects against NAFLD progression through the activation of AMPK signaling pathways.


Subject(s)
Adenosine Deaminase , Diet, High-Fat , Mice, Knockout , Non-alcoholic Fatty Liver Disease , RNA-Binding Proteins , Signal Transduction , Animals , Adenosine Deaminase/metabolism , Adenosine Deaminase/genetics , Adenosine Deaminase/deficiency , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , Mice , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/etiology , Diet, High-Fat/adverse effects , Male , AMP-Activated Protein Kinases/metabolism , AMP-Activated Protein Kinases/genetics , Insulin Resistance , Mice, Obese , Obesity/metabolism , Obesity/genetics , Mice, Inbred C57BL , Liver/metabolism
9.
Inflammation ; 2024 May 31.
Article in English | MEDLINE | ID: mdl-38819583

ABSTRACT

In this study, we investigated the role of hypoxia in the development of chronic inflammatory bowel disease (IBD), focusing on its impact on the HIF-1α signaling pathway through the upregulation of lipocalin 2 (LCN2). Using a murine model of colitis induced by sodium dextran sulfate (DSS) under hypoxic conditions, transcriptome sequencing revealed LCN2 as a key gene involved in hypoxia-mediated exacerbation of colitis. Bioinformatics analysis highlighted the involvement of crucial pathways, including HIF-1α and glycolysis, in the inflammatory process. Immune infiltration analysis demonstrated the polarization of M1 macrophages in response to hypoxic stimulation. In vitro studies using RAW264.7 cells further elucidated the exacerbation of inflammation and its impact on M1 macrophage polarization under hypoxic conditions. LCN2 knockout cells reversed hypoxia-induced inflammatory responses, and the HIF-1α pathway activator dimethyloxaloylglycine (DMOG) confirmed LCN2's role in mediating inflammation via the HIF-1α-induced glycolysis pathway. In a DSS-induced colitis mouse model, oral administration of LCN2-silencing lentivirus and DMOG under hypoxic conditions validated the exacerbation of colitis. Evaluation of colonic tissues revealed altered macrophage polarization, increased levels of inflammatory factors, and activation of the HIF-1α and glycolysis pathways. In conclusion, our findings suggest that hypoxia exacerbates colitis by modulating the HIF-1α pathway through LCN2, influencing M1 macrophage polarization in glycolysis. This study contributes to a better understanding of the mechanisms underlying IBD, providing potential therapeutic targets for intervention.

10.
Cell Signal ; 120: 111187, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38648894

ABSTRACT

Hypobaric hypoxia, commonly experienced at elevated altitudes, presents significant physiological challenges. Our investigation is centered on the impact of the bromodomain protein 4 (BRD4) under these conditions, especially its interaction with the Wnt/ß-Catenin pathway and resultant effects on glycolytic inflammation and intestinal barrier stability. By combining transcriptome sequencing with bioinformatics, we identified BRD4's key role in hypoxia-related intestinal anomalies. Clinical parameters of altitude sickness patients, including serum BRD4 levels, inflammatory markers, and barrier integrity metrics, were scrutinized. In vitro studies using CCD 841 CoN cells depicted expression changes in BRD4, Interleukin (IL)-1ß, IL-6, and ß-Catenin. Transepithelial electrical resistance (TEER) and FD4 analyses assessed barrier resilience. Hypoxia-induced mouse models, analyzed via H&E staining and Western blot, provided insights into barrier and protein alterations. Under hypoxic conditions, marked BRD4 expression variations emerged. Elevated serum BRD4 in patients coincided with intensified Wnt signaling, inflammation, and barrier deterioration. In vitro, findings showed hypoxia-induced upregulation of BRD4 and inflammatory markers but a decline in Occludin and ZO1, affecting barrier strength-effects mitigated by BRD4 inhibition. Mouse models echoed these patterns, linking BRD4 upregulation in hypoxia to barrier perturbations. Hypobaric hypoxia-induced BRD4 upregulation disrupts the Wnt/ß-Catenin signaling, sparking glycolysis-fueled inflammation and weakening intestinal tight junctions and barrier degradation.


Subject(s)
Transcription Factors , Wnt Signaling Pathway , Adult , Animals , Female , Humans , Male , Mice , Altitude Sickness/metabolism , beta Catenin/metabolism , Bromodomain Containing Proteins , Cell Cycle Proteins/metabolism , Hypoxia/metabolism , Inflammation/metabolism , Intestinal Mucosa/metabolism , Mice, Inbred C57BL , Transcription Factors/metabolism
11.
J Nanobiotechnology ; 22(1): 160, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38589911

ABSTRACT

Dry eye disease (DED) is associated with ocular hyperosmolarity and inflammation. The marketed topical eye drops for DED treatment often lack bioavailability and precorneal residence time. In this study, we investigated catechol-functionalized polyzwitterion p(MPC-co-DMA), composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) and dopamine methacrylamide (DMA) monomers, as potential topical nanotherapeutics for DED. The copolymers were synthesized via random free-radical copolymerization, producing different proportions of catecholic functionalization. All as-prepared polymer compositions displayed good ocular biocompatibility. At a feeding ratio of 1:1, p(MPC1-co-DMA1) can facilitate a robust mucoadhesion via Michael addition and/or Schiff base reaction, thus prolonging ocular residence time after 4 days of topical instillation. The hydration lubrication of MPC and radical-scavenging DMA endow the nano-agent to ease tear-film hyperosmolarity and corneal inflammation. A single dose of p(MPC1-co-DMA1) (1 mg/mL) after 4 days post-instillation can protect the cornea against reactive oxygen species, inhibiting cell apoptosis and the over-expression of pro-inflammatory factors (IL-6 and TNF-α). In clinical assessment, DED-induced rabbit eyes receiving p(MPC1-co-DMA1) could increase lacrimal fluid secretion by 5-fold higher than cyclosporine A. The catechol-functionalized polyzwitterion with enhanced lubricity, mucoadhesion, and anti-oxidation/anti-inflammation properties has shown high promise as a bioactive eye drop formulation for treating DED.


Subject(s)
Antioxidants , Lubricants , Animals , Rabbits , Antioxidants/pharmacology , Biocompatible Materials , Anti-Inflammatory Agents , Ophthalmic Solutions , Catechols , Inflammation
12.
Article in English | MEDLINE | ID: mdl-38613619

ABSTRACT

The formulation of more accurate models to describe tissue mechanics necessitates the availability of tools and instruments that can precisely measure the mechanical response of tissues to physical loads and other stimuli. In this regard, neuroscience has trailed other life sciences owing to the unavailability of representative live tissue models and deficiency of experimentation tools. We previously addressed both challenges by employing a novel instrument called the cantilevered-capillary force apparatus (CCFA) to elucidate the mechanical properties of mouse neurospheres under compressive forces. The neurospheres were derived from murine stem cells, and our study was the first of its kind to investigate the viscoelasticity of living neural tissues in vitro. In the current study, we demonstrate the utility of the CCFA as a broadly applicable tool to evaluate tissue mechanics by quantifying the effect that oxidative stress has on the mechanical properties of neurospheres. We treated mouse neurospheres with non-cytotoxic levels of hydrogen peroxide and subsequently evaluated the storage and loss moduli of the tissues under compression and tension. We observed that the neurospheres exhibit viscoelasticity consistent with neural tissue and show that elastic modulus decreases with increasing size of the neurosphere. Our study yields insights for establishing rheological measurements as biomarkers by laying the groundwork for measurement techniques and showing that the influence of a particular treatment may be misinterpreted if the size dependence is ignored.

13.
Opt Express ; 32(7): 12340-12357, 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38571059

ABSTRACT

Considerable efforts have been devoted to augmented reality (AR) displays to enable the immersive user experience in the wearable glasses form factor. Transparent waveguide combiners offer a compact solution to guide light from the microdisplay to the front of eyes while maintaining the see-through optical path to view the real world simultaneously. To deliver a realistic virtual image with low power consumption, the waveguide combiners need to have high efficiency and good image quality. One important limiting factor for the efficiency of diffractive waveguide combiners is the out-coupling problem in the input couplers, where the guided light interacts with the input gratings again and get partially out-coupled. In this study, we introduce a theoretical model to deterministically find the upper bound of the input efficiency of a uniform input grating, constrained only by Lorentz reciprocity and energy conservation. Our model considers the polarization management at the input coupler and can work for arbitrary input polarization state ensemble. Our model also provides the corresponding characteristics of the input coupler, such as the grating diffraction efficiencies and the Jones matrix of the polarization management components, to achieve the optimal input efficiency. Equipped with this theoretical model, we investigate how the upper bound of input efficiency varies with geometric parameters including the waveguide thickness, the projector pupil size, and the projector pupil relief distance. Our study shines light on the fundamental efficiency limit of input couplers in diffractive waveguide combiners and highlights the benefits of polarization control in improving the input efficiency.

14.
Nanoscale ; 16(18): 9075-9083, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38639490

ABSTRACT

Achieving control over symmetry breaking of completely achiral components in the aqueous phase is a significant challenge in supramolecular chemistry. Herein, we demonstrate that it is possible to construct chiral nanoassemblies by introducing metal ions (Zn2+, Fe3+, Al3+, Cu2+, and Ca2+) into completely achiral azobenzene amphiphiles with key structural factors in the pure aqueous phase. It is found that the coordination interactions, π-π stacking, hydrophilic and hydrophobic interactions, hydrogen bonding, and electrostatic interactions are crucial to the metal-ion-induced symmetry breaking of completely achiral building blocks. This study may provide an intriguing model system for constructing chiral assemblies based on completely achiral molecules.

15.
Expert Rev Clin Pharmacol ; 17(5-6): 455-465, 2024.
Article in English | MEDLINE | ID: mdl-38626303

ABSTRACT

INTRODUCTION: Opioids are commonly used for perioperative analgesia, yet children still suffer high rates of severe post-surgical pain and opioid-related adverse effects. Persistent and severe acute surgical pain greatly increases the child's chances of chronic surgical pain, long-term opioid use, and opioid use disorder. AREAS COVERED: Enhanced recovery after surgery (ERAS) protocols are often inadequate in treating a child's severe surgical pain. Research suggests that 'older' and longer-acting opioids such as methadone are providing better methods to treat acute post-surgical pain. Studies indicate that lower repetitive methadone doses can decrease the incidence of chronic persistent surgical pain (CPSP). Ongoing research explores genetic components influencing severe surgical pain, inadequate opioid analgesia, and opioid use disorder. This new genetic research coupled with better utilization of opioids in the perioperative setting provides hope in personalizing surgical pain management, reducing pain, opioid use, adverse effects, and helping the fight against the opioid pandemic. EXPERT OPINION: The opioid and analgesic pharmacogenomics approach can proactively 'tailor' a perioperative analgesic plan to each patient based on underlying polygenic risks. This transition from population-based knowledge of pain medicine to individual patient knowledge can transform acute pain medicine and greatly reduce the opioid epidemic's socioeconomic, personal, and psychological strains globally.


Subject(s)
Analgesics, Opioid , Chronic Pain , Opioid-Related Disorders , Pain, Postoperative , Pharmacogenetics , Humans , Pain, Postoperative/drug therapy , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/adverse effects , Child , Opioid-Related Disorders/prevention & control , Chronic Pain/drug therapy , Pain Management/methods , Perioperative Care/methods , Acute Pain/drug therapy , Methadone/administration & dosage , Methadone/adverse effects , Precision Medicine/methods , Severity of Illness Index , Dose-Response Relationship, Drug , Enhanced Recovery After Surgery
16.
BMC Psychol ; 12(1): 115, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38429641

ABSTRACT

OBJECTIVE: To analyze factors influencing the service experience of magnetic resonance imaging (MRI) examination and psychological status of patients admitted to a hospital and propose targeted solutions, and optimize the examination process and nursing by analyzing the MRI examination experience and psychological effect on patients. METHODS: The MRI examination rooms of two tertiary general hospitals in Haikou City were sampled at random, and 206 patients who met the study criteria were surveyed on site. RESULTS: (1) The item with the lowest mean score for patient examination services was whether earplugs were provided to the patient during the examination (B8 = 0.47). (2) Environmental logistics experience (16.83 ± 3.036) received the lowest score among the three service experience dimensions. (3) The average anxiety score of the patients was 5.38. (4) There was a positive correlation between the examination experience and the examination service experience of the patients. (5) Patients with higher monthly income had decreased anxiety (coefficient = -2.334), and MRI examination of the extremities relieved the anxiety (coefficient = -4.782). CONCLUSION: The environmental logistics factors, poor service attitude, examination site, and income were the most significant factors affecting the MRI examination experience and psychological status of patients, which can be improved by providing information, enhancing the waiting environment, providing targeted patient education, and evaluating the experience immediately.


Subject(s)
Anxiety , Magnetic Resonance Imaging , Humans , Surveys and Questionnaires , Anxiety Disorders
17.
Opt Express ; 32(5): 6814-6822, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38439378

ABSTRACT

We propose and experimentally demonstrate for the first time up to the authors' knowledge a wide field-of-view (FOV) water-to-air optical transmission using rolling-shutter (RS) based optical camera communication (OCC). Here, we evaluate the proposed OCC system without water ripple and with different percentage increases of water ripple. Long short term memory neural network (LSTM-NN) is utilized to mitigate the wavy water turbulence induced link outage and to decode 4-level pulse-amplitude-modulation (PAM4) RS pattern by meeting the pre-forward error correction bit-error-rate (pre-FEC BER = 3.8 × 10-3). We also evaluate the FOVs of the proposed water-to-air RS-based OCC system. This can be implemented by using different angular rotations of the camera. Experimental results show that the proposed OCC system can support ±70°, ± 30°, and ±30° rotations around the z-, y- and x-directions, respectively when operated at 6 kbit/s and decoded using LSTM-NN.

18.
Saudi Pharm J ; 32(4): 101980, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38439949

ABSTRACT

Xanthine oxidase (XO) has been widely recognized as a pivotal enzyme in developing hyperuricemia, primarily contributing to the excessive production of uric acid during purine metabolism in the liver. One of the standard treatment approaches involves reducing uric acid levels by inhibiting XO activity. In this study, the leaf extract of Dolichandrone spathacea, traditionally used in folk medicine, was found to inhibit XO activity in the ethyl acetate and butanol fractions at a concentration of 100 µg/mL, their values were 78.57 ± 3.85 % (IC50 = 55.93 ± 5.73 µg/ml) and 69.43 ± 8.68 % (IC50 = 70.17 ± 7.98 µg/ml), respectively. The potential XO inhibitory components were isolated by bioactivity assays and the HR-ESI-MS and NMR spectra system. The main constituents of leaf extracts of Dolichandrone spathacea, six compounds, namely trans-4-methoxycinnamic acid (3), trans-3,4-dimethoxycinnamic acid (4), p-coumaric acid (5), martynoside (6), 6-O-(p-methoxy-E-cinnamoyl)-ajugol (7), and scolymoside (17), were identified as potent XO inhibitors with IC50 values ranging from 19.34 ± 1.63 µM to 64.50 ± 0.94 µM. The enzyme kinetics indicated that compounds 3-5, 7, and 17 displayed competitive inhibition like allopurinol, while compound 6 displayed a mixed-type inhibition. Computational studies corroborated these experimental results, highlighting the interactions between potential metabolites and XO enzyme. The hydrogen bonds played crucial roles in the binding interaction, especially, scolymoside (17) forms a hydrogen bond with Mos3004, exhibited the lowest binding energy (-18.3286 kcal/mol) corresponding to the lowest IC50 (19.34 ± 1.63 µM). Furthermore, nine compounds were isolated for the first time from this plant. In conclusion, Dolichandrone spathacea and its constituents possess the potential to modulate the xanthine oxidase enzyme involved in metabolism.

19.
Int J Biol Macromol ; 265(Pt 2): 130945, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38493818

ABSTRACT

INTRODUCTION: Immune checkpoint inhibitor therapy is a highly promising strategy for clinical treatment of cancer. Among these inhibitors, ipilimumab stands out for its ability to induce cytotoxic T cell proliferation and activation by binding to CTLA-4. However, ipilimumab also gives rise to systemic immune-related adverse effects and tumor immune evasion, limiting its effectiveness. OBJECTIVES: We developed IFNγ-ipilimumab and confirmed that the addition of INF-γ does not alter the fundamental properties of ipilimumab. RESULTS: IFNγ-ipilimumab can be activated by matrix metalloproteinases, thereby promoting the IFNγ signaling pathway and enhancing the cytotoxicity of T cells. In vivo studies demonstrated that IFNγ-ipilimumab enhances the therapeutic effect of ipilimumab against colorectal cancer by increasing CD8+ and CD4+ lymphocyte infiltration into the tumor area and inducing MHC-I expression in tumor cells. Mice treated with IFNγ-ipilimumab showed higher survival rates and body weight, as well as lower CD4+ and CD8+ lymphocyte activation rates in the blood and reduced organ damage. CONCLUSION: IFNγ-ipilimumab improved the effectiveness of ipilimumab while reducing its side effects. It is likely that future immunotherapies would rely on such antibodies to activate local cancer cells or immune cells, thereby increasing the therapeutic effectiveness of cancer treatments and ensuring their safety.


Subject(s)
Antineoplastic Agents , Neoplasms , Animals , Mice , Ipilimumab/pharmacology , Ipilimumab/therapeutic use , Antibodies, Monoclonal/adverse effects , Antineoplastic Agents/pharmacology , Neoplasms/drug therapy , T-Lymphocytes, Cytotoxic
20.
J Robot Surg ; 18(1): 88, 2024 Feb 22.
Article in English | MEDLINE | ID: mdl-38386236

ABSTRACT

Transoral vestibular robotic thyroidectomy can really make the patient's body surface free of scar. This study aimed to compare the surgical and patient-related outcomes between the transoral vestibular robotic thyroidectomy and traditional low-collar incision thyroidectomy. The clinical data of 120 patients underwent transoral vestibular robotic thyroidectomy (TOVRT) or traditional low-collar incision thyroidectomy (TLCIT) were collected from May 2020 to October 2021. Propensity score matching analysis was used to minimize selection bias. All these patients were diagnosed with papillary thyroid carcinoma (PTC) through ultrasound-guided fine-needle aspiration prior to surgical intervention and surgical plan was tailored for each patient. An intraoperative recurrent laryngeal nerve (RLN) detection system was used in all patients, whose RLNs were identified and protected. We performed transoral vestibular robotic thyroidectomy with three intraoral incisions. Additional right axillary fold incisions were adopted occasionally to enhance fine reverse traction of tissue for radical tumor dissection. Clinical data including gender, age, tumor size, BMI, operation time, postoperative drainage volume and time, pain score, postoperative length of stay (LOS),number of lymph nodes removed, complications, and medical expense were observed and analyzed. Propensity score matching was used for 1:1 matching between the TOVRT group and the TLCIT group. All these patients accepted total thyroidectomy(or lobectomy) plus central lymph node dissection and all suffered from PTC confirmed by postoperative pathology. No conversion to open surgery happened in TOVRT group. The operative time of TOVRT group was longer than that of TLCIT group (P < 0.05). The postoperative drainage volume of TOVRT group was more than that of TLCIT group (P < 0.05). The drainage tube placement time of TOVRT group were longer than that of TLCIT group (P < 0.05). Significant differences were also found in intraoperative bleeding volume, pain score and medical expense between the two groups (P < 0.05). The incidence of perioperative common complications such as hypoparathyroidism and vocal cord paralysis in the two groups was almost identical (P > 0.05). However, there were some specific complications such as surgical area infection (one case), skin burn (one case), oral tear (two cases), and paresthesia of the lower lip and the chin (two cases) were found in TOVRT group. Obviously, the postoperative cosmetic effect of the TOVRT group was better than TLCIT group (P < 0.05). TOVRT is safe and feasible for low to moderate-risk PTC patients and is a potential alternative for patients who require no scar on their neck. Patients accepted TOVRT can get more satisfaction and have less psychologic injury caused by surgery.


Subject(s)
Neoplasms , Robotic Surgical Procedures , Humans , Thyroidectomy/adverse effects , Robotic Surgical Procedures/methods , Drainage , Cicatrix , Pain
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