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1.
J Nanobiotechnology ; 22(1): 383, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38951875

ABSTRACT

The characteristic features of the rheumatoid arthritis (RA) microenvironment are synovial inflammation and hyperplasia. Therefore, there is a growing interest in developing a suitable therapeutic strategy for RA that targets the synovial macrophages and fibroblast-like synoviocytes (FLSs). In this study, we used graphene oxide quantum dots (GOQDs) for loading anti-arthritic sinomenine hydrochloride (SIN). By combining with hyaluronic acid (HA)-inserted hybrid membrane (RFM), we successfully constructed a new nanodrug system named HA@RFM@GP@SIN NPs for target therapy of inflammatory articular lesions. Mechanistic studies showed that this nanomedicine system was effective against RA by facilitating the transition of M1 to M2 macrophages and inhibiting the abnormal proliferation of FLSs in vitro. In vivo therapeutic potential investigation demonstrated its effects on macrophage polarization and synovial hyperplasia, ultimately preventing cartilage destruction and bone erosion in the preclinical models of adjuvant-induced arthritis and collagen-induced arthritis in rats. Metabolomics indicated that the anti-arthritic effects of HA@RFM@GP@SIN NPs were mainly associated with the regulation of steroid hormone biosynthesis, ovarian steroidogenesis, tryptophan metabolism, and tyrosine metabolism. More notably, transcriptomic analyses revealed that HA@RFM@GP@SIN NPs suppressed the cell cycle pathway while inducing the cell apoptosis pathway. Furthermore, protein validation revealed that HA@RFM@GP@SIN NPs disrupted the excessive growth of RAFLS by interfering with the PI3K/Akt/SGK/FoxO signaling cascade, resulting in a decline in cyclin B1 expression and the arrest of the G2 phase. Additionally, considering the favorable biocompatibility and biosafety, these multifunctional nanoparticles offer a promising therapeutic approach for patients with RA.


Subject(s)
Arthritis, Rheumatoid , Cell Proliferation , Graphite , Macrophages , Morphinans , Quantum Dots , Synoviocytes , Morphinans/pharmacology , Morphinans/chemistry , Animals , Quantum Dots/chemistry , Quantum Dots/therapeutic use , Arthritis, Rheumatoid/drug therapy , Synoviocytes/drug effects , Synoviocytes/metabolism , Graphite/chemistry , Graphite/pharmacology , Cell Proliferation/drug effects , Rats , Macrophages/drug effects , Macrophages/metabolism , Fibroblasts/drug effects , Fibroblasts/metabolism , Male , Arthritis, Experimental/drug therapy , Arthritis, Experimental/pathology , Rats, Sprague-Dawley , Mice , Humans , RAW 264.7 Cells , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology
2.
ACS Appl Mater Interfaces ; 16(26): 34020-34029, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961571

ABSTRACT

Rechargeable aqueous Zn-ion batteries with a Zn anode hold great promise as promising candidates for advanced energy storage systems. The construction of protective layer coatings on Zn anode is an effective way to suppress the growth of Zn dendrites and water-induced side reactions. Herein, we reported a series of UIO-66 materials with different concentrations of reduced graphene oxide (rG) coated onto the surface of Zn foil (Zn@UIO-66/rGx; x = 0.05, 0.1, and 0.2). Benefiting from the synergistic effect of UIO-66 and rG, symmetric cells with Zn@UIO-66/rGx (x = 0.1) electrodes exhibit excellent reversibility (e.g., long cycling life over 1100 h at 1 mA cm-2/1 mAh cm-2) and superior rate capability (e.g., over 1100 and 400 h at 5 mA cm-2/2.5 mAh cm-2 and 10 mA cm-2/5 mAh cm-2, respectively). When the Zn@UIO-66/rG0.1 anode was paired with the NaV3O8·1.5H2O (NVO) cathode, the Zn@UIO-66/rG0.1||NVO cell also delivered a high reversible capacity of 189.9 mAh g-1 with an initial capacity retention of 61.3% after 500 cycles at 1 A g-1, compared to the bare Zn||NVO cell with only 92 cycles.

3.
Int J Biol Macromol ; 275(Pt 2): 133608, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38960249

ABSTRACT

Lutein, a natural pigment with multiple beneficial bioactivities, faces limitations in food processing due to its instability. In this study, we constructed four modified walnut protein isolate (WNPI) based emulsions as emulsion-based delivery systems (EBDS) for lutein fortification. The modification treatments enhanced the encapsulation efficiency of the WNPI-based EBDS on lutein. The modified WNPI-based EBDS exhibited improved storage and digestive stability, as well as increased lutein delivery capability in simulated gastrointestinal conditions. After in vitro digestion, the lutein retention in the modified WNPI-based EBDS was higher than in the untreated WNPI-based EBDS, with a maximum retention of 49.67 ± 1.10 % achieved after ultrasonic modification. Furthermore, the modified WNPI-based EBDS exhibited an elevated lutein bioaccessibility, reaching a maximum value of 40.49 ± 1.29 % after ultrasonic modification, nearly twice as high as the untreated WNPI-based EBDS. Molecular docking analysis indicated a robust affinity between WNPI and lutein, involving hydrogen bonds and hydrophobic interactions. Collectively, this study broadens WNPI's application and provides a foundation for fortifying other fat-soluble bioactive substances.

4.
Discov Oncol ; 15(1): 266, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38967893

ABSTRACT

Glioma is the most common malignant tumor in the central nervous system, and its unique pathogenesis often leads to poor treatment outcomes and prognosis. In 2021, the World Health Organization (WHO) divided gliomas into five categories based on their histological characteristics and molecular changes. Non-coding RNA is a type of RNA that does not encode proteins but can exert biological functions at the RNA level, and long non-coding RNA (lncRNA) is a type of non-coding RNA with a length exceeding 200 nt. It is controlled by various transcription factors and plays an indispensable role in the regulatory processes in various cells. Numerous studies have confirmed that the dysregulation of lncRNA is critical in the pathogenesis, progression, and malignancy of gliomas. Therefore, this article reviews the proliferation, apoptosis, invasion, migration, angiogenesis, immune regulation, glycolysis, stemness, and drug resistance changes caused by the dysregulation of lncRNA in gliomas, and summarizes their potential clinical significance in gliomas.

5.
ACS Omega ; 9(26): 28129-28143, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38973879

ABSTRACT

An efficient and mild protocol for the visible light-induced radical cascade difluoromethylation/cyclization of imidazoles with unactivated alkenes using easily accessible and bench-stable difluoromethyltriphenylphosphonium bromide as the precursor of the -CF2H group has been developed to afford CF2H-substituted polycyclic imidazoles in moderate to good yields. This strategy, along with the construction of Csp3-CF2H/C-C bonds, is distinguished by mild conditions, no requirement of additives, simple operation, and wide substrate scope. In addition, the mechanistic experiments have indicated that the difluoromethyl radical pathway is essential for the methodology.

7.
Article in English | MEDLINE | ID: mdl-38980408

ABSTRACT

For acute ischemic stroke treatment, the limitations of treatment methods and the high incidence of perioperative complications seriously affect the survival rate and postoperative recovery of patients. Human umbilical cord mesenchymal stem cells (hucMSCs) have multi-directional differentiation potential and immune regulation function, which is a potential cell therapy. The present investigation involved developing a model of cerebral ischemia-reperfusion injury by thrombectomy after middle cerebral artery occlusion (MCAO) for 90 min in rats and utilizing comprehensive multi-system evaluation methods, including the detection of brain tissue ischemia, postoperative survival rate, neurological score, anesthesia recovery monitoring, pain evaluation, stress response, and postoperative pulmonary complications, to elucidate the curative effect of tail vein injection of hucMSCs on MCAO's perioperative complications. Based on our research, it has been determined that hucMSCs treatment can reduce the volume of brain tissue ischemia, promote the recovery of neurological function, and improve the postoperative survival rate of MCAO in rats. At the same time, hucMSCs treatment can prolong the time of anesthesia recovery, relieve the occurrence of delirium during anesthesia recovery, and also have a good control effect on postoperative weight loss, facial pain expression, and lung injury. It can also reduce postoperative stress response by regulating blood glucose and serum levels of stress-related proteins including TNF-α, IL-6, CRP, NE, cortisol, ß-endorphin, and IL-10, and ultimately promote the recovery of MCAO's perioperative complications.

8.
Cancer Med ; 13(14): e70011, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39001676

ABSTRACT

OBJECTIVE: Immunotherapy, specifically immune checkpoint inhibitors (ICIs), has revolutionized cancer treatment. However, it can also cause immune-related adverse events (irAEs). This study aimed to develop a clinically practical animal model of irAEs using BALB/c mice. METHODS: Subcutaneous tumors of mouse breast cancer 4T1 cells were generated in inbred BALB/c mice. The mice were treated with programmed death-1 (PD-1) and cytotoxic t-lymphocyte antigen 4 (CTLA-4) inhibitors once every 3 days for five consecutive administration cycles. Changes in tumor volume and body weight were recorded. Lung computed tomography (CT) scans were conducted. The liver, lungs, heart, and colon tissues of the mice were stained with hematoxylin-eosin (H&E) staining to observe inflammatory infiltration and were scored. Serum samples were collected, and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of ferritin, glutamic-pyruvic transaminase (ALT), tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ), and interleukin-6 (IL-6). Mouse liver and lung cell suspensions were prepared, and changes in macrophages, T cells, myeloid-derived suppressor cells (MDSCs), and regulatory (Treg) cells were detected by flow cytometry. RESULTS: Mice treated with PD-1 and CTLA-4 inhibitors showed significant reductions in tumor volume and body weight. The tissue inflammatory scores in the experimental group were significantly higher than those in the control group. Lung CT scans of mice in the experimental group showed obvious inflammatory spots. Serum levels of ferritin, IL-6, TNF-α, IFN-γ, and ALT were significantly elevated in the experimental group. Flow cytometry analysis revealed a substantial increase in CD3+T cells, Treg cells, and macrophages in the liver and lung tissues of mice in the experimental group compared with the control group, and the change trend of MDSCs was opposite. CONCLUSIONS: The irAE-related animal model was successfully established in BALB/c mice using a combination of PD-1 and CTLA-4 inhibitors through multiple administrations with clinical translational value and practical. This model offers valuable insights into irAE mechanisms for further investigation.


Subject(s)
Disease Models, Animal , Immune Checkpoint Inhibitors , Mice, Inbred BALB C , Animals , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/pharmacology , Mice , Female , CTLA-4 Antigen/antagonists & inhibitors , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Cell Line, Tumor
9.
iScience ; 27(7): 110228, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-38993673

ABSTRACT

Colorectal cancer (CRC) is a prevalent cancer with intraperitoneal free cancer cells (IFCCs) playing a significant role in prognosis, especially during surgeries. The identification of IFCCs is crucial for determining the stage and treatment of patients with CRC. Existing methods for IFCC detection, such as conventional cytology, immunocytochemistry (ICC), and polymerase chain reaction (PCR), have limitations in sensitivity and specificity. This study investigates the potential of long noncoding RNA (lncRNA) SNHG1 as a biomarker for detecting IFCCs in patients with CRC. Testing on a cohort of 91 patients with CRC and 26 patients with gastrointestinal benign disease showed that SNHG1 outperformed CEA in distinguishing CRC cells and detecting IFCCs across different disease stages. SNHG1 demonstrated higher sensitivity (76.1% vs. 43.1%) and specificity (68.4% vs. 52.3%) than CEA for IFCC detection in patients with CRC, suggesting its promising role as a clinical method for identifying IFCCs in CRC.

10.
Angew Chem Int Ed Engl ; : e202402635, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38981858

ABSTRACT

Ammonia is a promising candidate in the quest for sustainable, clean energy. With its capacity to serve as an energy carrier, the oxidation of ammonia opens avenues for carbon-neutral approaches to address worldwide growing energy needs. We report the catalytic chemical oxidation of ammonia by an Earth-abundant transition metal complex, trans-[LFeII(MeCN)2][PF6]2, where L is a macrocyclic ligand bearing four N-heterocyclic carbene (NHC) donors. Using triarylaminium radical cations in MeCN, up to 182 turnovers of N2 per Fe were obtained from chemical catalysis with an extremely low loading of the Fe catalyst (0.043 mM, 0.004 mol % catalyst). This chemical catalysis was successfully transitioned to mediated electrocatalysis for the oxidation of ammonia. Molecular electrocatalysis by the Fe catalyst and the mediator (p-MeOC6H4)3N exhibited a catalytic half-wave potential (Ecat/2) of 0.18 V vs [Cp2Fe]+/0 in MeCN, and achieved 9.3 turnovers of N2 at an applied potential of 0.20 V vs [Cp2Fe]+/0 at -20 °C in controlled-potential electrolysis, with a Faradaic efficiency of 75%. Based on computational results, the catalyst undergoes sequential oxidation and deprotonation steps to form [LFeIV(NH2)2]2+, and thereafter bimetallic coupling to form an N-N bond.

11.
Neurochem Res ; 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39023805

ABSTRACT

This study aimed to assess the impact of conditioned medium from epidermal neural crest stem cells (EPI-NCSCs-CM) on functional recovery following spinal cord injury (SCI), while also exploring the involvement of the PI3K-AKT signaling pathway in regulating neuronal apoptosis. EPI-NCSCs were isolated from 10-day-old Sprague-Dawley rats and cultured for 48 h to obtain EPI-NCSC-CM. SHSY-5Y cells were subjected with H2O2 treatment to induce apoptosis. Cell viability and survival rates were evaluated using the CCK-8 assay and calcein-AM/PI staining. SCI contusion model was established in adult Sprague-Dawley rats to assess functional recovery, utilizing the Basso, Beattie and Bresnahan (BBB) scoring system, inclined test, and footprint observation. Neurological restoration after SCI was analyzed through electrophysiological recordings. Histological analysis included hematoxylin and eosin (H&E) staining and Nissl staining to evaluate tissue organization. Apoptosis and oxidative stress levels were assessed using TUNEL staining and ROS detection methods. Additionally, western blotting was performed to examine the expression of apoptotic markers and proteins related to the PI3K/AKT signaling pathway. EPI-NCSC-CM significantly facilitated functional and histological recovery in SCI rats by inhibiting neuronal apoptosis through modulation of the PI3K/AKT pathway. Administration of EPI-NCSCs-CM alleviated H2O2-induced neurotoxicity in SHSY-5Y cells in vitro. The use of LY294002, a PI3K inhibitor, underscored the crucial role of the PI3K/AKT signaling pathway in regulating neuronal apoptosis. This study contributes to the ongoing exploration of molecular pathways involved in spinal cord injury (SCI) repair, focusing on the therapeutic potential of EPI-NCSC-CM. The research findings indicate that EPI-NCSC-CM exerts a neuroprotective effect by suppressing neuronal apoptosis through activation of the PI3K/AKT pathway in SCI rats. These results highlight the promising role of EPI-NCSC-CM as a potential treatment strategy for SCI, emphasizing the significance of the PI3K/AKT pathway in mediating its beneficial effects.

12.
Gut ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38955401

ABSTRACT

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy because it is often diagnosed at a late-stage. Signal transducer and activator of transcription 5 (STAT5) is a transcription factor implicated in the progression of various cancer types. However, its role in KRAS-driven pancreatic tumourigenesis remains unclear. DESIGN: We performed studies with LSL-Kras G12D; Ptf1a-Cre ERT (KCERT) mice or LSL-KrasG12D; LSL-Trp53R172H ; Pdx1-Cre (KPC) mice crossed with conditional disruption of STAT5 or completed deficiency interleukin (IL)-22. Pancreatitis was induced in mice by administration of cerulein. Pharmacological inhibition of STAT5 on PDAC prevention was studied in the orthotopic transplantation and patient-derived xenografts PDAC model, and KPC mice. RESULTS: The expression and phosphorylation of STAT5 were higher in human PDAC samples than control samples and high levels of STAT5 in tumour cells were associated with a poorer prognosis. The loss of STAT5 in pancreatic cells substantially reduces the KRAS mutation and pancreatitis-derived acinar-to-ductal metaplasia (ADM) and PDAC lesions. Mechanistically, we discovered that STAT5 binds directly to the promoters of ADM mediators, hepatocyte nuclear factor (HNF) 1ß and HNF4α. Furthermore, STAT5 plays a crucial role in maintaining energy metabolism in tumour cells during PDAC progression. IL-22 signalling induced by chronic inflammation enhances KRAS-mutant-mediated STAT5 phosphorylation. Deficiency of IL-22 signalling slowed the progression of PDAC and ablated STAT5 activation. CONCLUSION: Collectively, our findings identified pancreatic STAT5 activation as a key downstream effector of oncogenic KRAS signalling that is critical for ADM initiation and PDAC progression, highlighting its potential therapeutic vulnerability.

13.
J Tissue Viability ; 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38964979

ABSTRACT

BACKGROUND: This pilot study assessed text messaging as an early intervention for preventing pressure ulcers (PrUs) in individuals with spinal cord injury (SCI) post-hospital discharge. METHOD: Thirty-nine wheelchair-users discharged after acquiring a SCI, underwent randomisation into an intervention group (n = 20) with text messages and a control group (n = 19). All participants received standard post-discharge care and completed a skincare questionnaire before and 6-month after discharge. Primary outcomes included feasibility and acceptability of early intervention using text messaging, alongside performance, concordance, and attitudes toward skincare. Secondary outcomes measured perception and the incidence of PrUs. RESULTS: Baseline demographics were comparable between the intervention and control groups. Eight of 20 participants completed 6-month follow-up questionnaires in the intervention group, six participants completed the 6-month questionnaires in the control group,. Participants expressed high satisfaction with text messages, understanding of content, and increased confidence in preventing PrUs. At 6-month post-discharge, the intervention group showed improved prevention practices, heightened awareness of PrU risks, and increased perceived importance of prevention, which were not observed in the control group. However, there were no significant differences in PrU incidence, possibly due to the small sample size and short follow-up. CONCLUSION: The study demonstrates that using text messaging as an early intervention for PrU prevention in individuals with SCI is feasible and well-received. Preliminary results suggest a positive impact on participants' attitudes and practices, indicating the potential of text messaging to reduce PrU incidence. However, further research with larger samples and extended follow-up is crucial to validate these promising initial findings.

14.
J Environ Manage ; 365: 121624, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38968888

ABSTRACT

In the context of global warming, the occurrence and severity of extreme events like atmospheric drought (AD) and warm spell duration index (WSDI) have increased, causing significant impacts on terrestrial ecosystems in Central Asia's arid regions. Previous research has focused on single extreme events such as AD and WSDI, but the effect of compound hot and dry events (CHWE) on grassland phenology in the arid regions of Central Asia remains unclear. This study utilized structural equation modeling (SEM) and the Pettitt breakpoint test to quantify the direct and indirect responses of grassland phenology (start of season - SOS, length of season - LOS, and end of season - EOS) to AD, WSDI, and CHWE. Furthermore, this research investigated the threshold of grassland phenology response to compound hot and dry events. The research findings indicate a significant increasing trend in AD, WSDI, and CHWE in the arid regions of Central Asia from 1982 to 2022 (0.51 day/year, P < 0.01; 0.25 day/year, P < 0.01; 0.26 day/year, P < 0.01). SOS in the arid regions of Central Asia showed a significant advancement trend, while EOS exhibited a significant advance. LOS demonstrated an increasing trend (-0.23 day/year, P < 0.01; -0.12 day/year, P < 0.01; 0.56 day/year). The temperature primarily governs the variation in SOS. While higher temperatures promote an earlier SOS, they also offset the delaying effect of CHWE on SOS. AD, temperature, and CHWE have negative impacts on EOS, whereas WSDI has a positive effect on EOS. AD exhibits the strongest negative effect on EOS, with an increase in AD leading to an earlier EOS. Temperature and WSDI are positively correlated with LOS, indicating that higher temperatures and increased WSDI contribute to a longer LOS. The threshold values for the response of SOS, EOS, and LOS to CHWE are 16.14, 18.49, and 16.61 days, respectively. When CHWE exceeds these critical thresholds, there are significant changes in the response of SOS, EOS, and LOS to CHWE. These findings deepen our understanding of the mechanisms by which extreme climate events influence grassland phenology dynamics in Central Asia. They can contribute to better protection and management of grassland ecosystems and help in addressing the impacts of global warming and climate change in practice.


Subject(s)
Droughts , Grassland , Seasons , Ecosystem , Climate Change , Asia , Global Warming
15.
Anal Methods ; 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38994818

ABSTRACT

Exosomal microRNAs (exomiRs) have been shown to play crucial roles as biomarkers for early detection and prognosis of cancer. However, simultaneous quantification of multiplex exomiRs is hindered by methods that require additional steps, such as labeling with fluorophores or gel visualization, which are susceptible to various factors. Herein, we developed a mass spectrometry-detectable and target-triggered method for multiplexed exomiR detection using three enzyme-based double recycling amplification in combination with well-designed molecular beacon-peptide (MBP) probes, called molecular beacon-peptide probe-based double recycling amplification (MBPDRA). MBP probes mediated the double recycling amplification reaction and were released as mass-detectable reporter peptides. In particular, the hybridization of the target microRNAs (miRNAs) with the stem-loop of the probe triggers two consecutive processes. The first cycle involved polymerase strand displacement amplification, leading to the production of complementary DNA (cycle I), and the second cycle encompassed the recycling exonuclease cleavage of the MBP probe (cycle II). Subsequently, excess probes were removed by interaction with streptavidin beads via biotin-streptavidin binding. The reporter peptides were released using trypsin and subsequently detected by mass spectrometry. Our method enables quantitative detection of multiple exomiRs with a dynamic range from 0.1 fM to 10 pM and a limit of quantification of 0.1 fM. Moreover, the proposed assay was successfully employed for quantification of three exomiRs, exmiR-21, exmiR-191, and exmiR-451a, in the sera of patients with pancreatic cancer. Based on these findings, we believe that the MBPDRA assay holds significant promise as a reliable method for quantifying multiple miRNAs in biomedical research and clinical diagnostics.

16.
Front Cell Infect Microbiol ; 14: 1394721, 2024.
Article in English | MEDLINE | ID: mdl-38975331

ABSTRACT

Since 2019, Coronavirus Disease 2019(COVID-19) has affected millions of people worldwide. Except for acute respiratory distress syndrome, dysgeusis is also a common symptom of COVID-19 that burdens patients for weeks or permanently. However, the mechanisms underlying taste dysfunctions remain unclear. Here, we performed complete autopsies of five patients who died of COVID-19. Integrated tongue samples, including numerous taste buds, salivary glands, vessels, and nerves were collected to map the pathology, distribution, cell tropism, and receptor distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the tongue. Our results revealed that all patients had moderate lymphocyte infiltration around the salivary glands and in the lamina propria adjacent to the mucosa, and pyknosis in the epithelia of taste buds and salivary glands. This may be because the serous acini, salivary gland ducts, and taste buds are the primary sites of SARS-CoV-2 infection. Multicolor immunofluorescence showed that SARS-CoV-2 readily infects Keratin (KRT)7+ taste receptor cells in taste buds, secretory cells in serous acini, and inner epithelial cells in the ducts. The major receptors, angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine subtype 2 (TMPRSS2), were both abundantly expressed in these cells. Viral antigens and receptor were both rarely detected in vessels and nerves. This indicates that SARS-CoV-2 infection triggers pathological injury in the tongue, and that dysgeusis may be directly related to viral infection and cellular damage.


Subject(s)
Angiotensin-Converting Enzyme 2 , Autopsy , COVID-19 , SARS-CoV-2 , Serine Endopeptidases , Tongue , Viral Tropism , Humans , COVID-19/pathology , COVID-19/virology , SARS-CoV-2/pathogenicity , Tongue/virology , Tongue/pathology , Male , Angiotensin-Converting Enzyme 2/metabolism , Female , Middle Aged , Serine Endopeptidases/metabolism , Salivary Glands/virology , Salivary Glands/pathology , Aged , Taste Buds/virology , Taste Buds/pathology , Receptors, Virus/metabolism
17.
Am J Ophthalmol ; 2024 Jul 13.
Article in English | MEDLINE | ID: mdl-39009239

ABSTRACT

PURPOSE: To measure low perfusion area (LPA) and focal perfusion loss (FPL) in the macula using OCT angiography (OCTA) for glaucoma. DESIGN: Prospective, cross-sectional "case-control" comparison study. METHODS: A total of 60 patients with primary open-angle glaucoma (POAG) and 37 normal participants were analyzed. AngioVue 6 × 6-mm high-definition (400 × 400 transverse pixels) macular OCTA scans were performed on one eye of each participant. Flow signal was calculated using the split-spectrum amplitude-decorrelation angiography algorithm. En face ganglion cell layer plexus (GCLP) and superficial vascular complex (SVC) images were generated. Using custom software, vessel density (VD) maps were obtained by computing the fraction of area occupied by flow pixels after low-pass filtering by local averaging 41 × 41 pixels. LPA was defined by local VD below 0.5 percentile over a contiguous area above 98.5 percentile of the normal reference population. The FPL was the percent VD loss (relative to normal mean) integrated over the LPA. RESULTS: Among patients with POAG, 30 had perimetric and 30 had pre-perimetric glaucoma. The LPAGCLP-VD was 0.16±0.38 mm2 in normal and 5.78±6.30 mm2 in glaucoma subjects (P<0.001). The FPLGCLP-VD was 0.20%±0.47% in normal and 7.52%±8.84% in glaucoma subjects (P<0.001). The perimetric glaucoma diagnostic accuracy, measured by the area under the receiver operating curve, was 0.993 for LPAGCLP-VD and 0.990 for FPLGCLP-VD. The sensitivities were 96.7% and 93.3% at 95% specificity, respectively. The LPAGCLP-VD and FPLGCLP-VD had good repeatability (0.957 and 0.952 by intraclass correlation coefficient). Diagnostic accuracy was better than GCLP VD (AROC 0.950, sensitivity 83.3%) and OCT ganglion cell complex (GCC) thickness (AROC 0.927, sensitivity 80.0%), GCC focal loss volume (AROC 0.957, sensitivity 80.0%). The LPAGCLP-VD and FPLGCLP-VD correlated well with central VF mean deviations (Pearson's r=-0.716 and -0.705 respectively, both P<0.001). CONCLUSION: Assessment of macular focal perfusion loss using OCTA is useful in evaluating glaucomatous damage.

18.
J Colloid Interface Sci ; 676: 197-206, 2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39024820

ABSTRACT

The efficient recycling of waste graphite anode from used lithium-ion batteries (LIBs) has attracted considerable concerns mainly owing to the environment protection and reutilization of resources. Herein, we reported a rational and facile strategy for the synthesis of holey graphite coated by carbon (hG0.01@C0.10) through the separation, purification and creation of holey structures of waste graphite by using NaOH and carbon-coating by using phenolic resin. The holey structures facilitate the hG0.01@C0.10 with the quick penetration of electrolytes and rapid diffusion of Li+. The carbon coating is more favorable for hG0.01@C0.10 with improved electronic conductivity and less alleviated volume during the cycles. Benefiting from the synergistic effect of holey structures and carbon coating, the hG0.01@C0.10 as anode for LIBs displays a high reversible capacity of 377.6 mAh g-1 at 0.5 C and superior rate capabilities (e.g., 348.0 and 274.7 mAh g-1 at 1 and 2 C, respectively) and maintains a high reversible capacity of 278.7 mAh g-1 at 1 C after 300 cycles with an initial capacity retention of 80.0 %.

20.
Int J Biol Macromol ; 273(Pt 2): 133063, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38880443

ABSTRACT

The oral delivery of doxorubicin (DOX), an anti-cancer drug, encounters multiple hurdles such as limited gastrointestinal permeability, P-glycoprotein-mediated efflux, brief intestinal residence, and rapid degradation. This study introduced a novel approach utilizing hyaluronic acid (HA)-grafted fatty acid monoglycerides (HGD) to encapsulate DOX, forming HGD-DOX nanoparticles, aimed at enhancing its oral bioavailability. Drug encapsulated by HGD provided several advantages, including extended drug retention in the gastrointestinal tract, controlled release kinetics, and promotion of lymphatic absorption in the intestine. Additionally, HGD-DOX nanoparticles could specifically target CD44 receptors, potentially increasing therapeutic efficacy. The uptake mechanism of HGD-DOX nanoparticles primarily involved clathrin-mediated, caveolin-mediated and macropinocytosis endocytosis. Pharmacokinetic analysis further revealed that HGD significantly prolonged the in vivo residence time of DOX. In vivo imaging and pharmacodynamic studies indicated that HGD possessed tumor-targeting capabilities and exhibited a significant inhibitory effect on tumor growth, while maintaining an acceptable safety profile. Collectively, these findings position HGD-DOX nanoparticles as a promising strategy to boost the oral bioavailability of DOX, offering a potential avenue for improved cancer treatment.


Subject(s)
Doxorubicin , Hyaluronan Receptors , Hyaluronic Acid , Nanoparticles , Doxorubicin/administration & dosage , Doxorubicin/chemistry , Doxorubicin/pharmacokinetics , Doxorubicin/pharmacology , Hyaluronic Acid/chemistry , Animals , Nanoparticles/chemistry , Hyaluronan Receptors/metabolism , Humans , Administration, Oral , Mice , Drug Carriers/chemistry , Cell Line, Tumor , Drug Delivery Systems , Xenograft Model Antitumor Assays
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