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1.
Rheumatol Ther ; 2024 Jun 09.
Article En | MEDLINE | ID: mdl-38853228

INTRODUCTION: Interleukin-17A (IL-17A) plays a crucial role in the pathogenesis of ankylosing spondylitis (AS), although not all patients respond to traditional IL-17A antibody treatments. QX002N injection, as a new monoclonal antibody targeting IL-17A, has shown potential in treating AS, offering a new treatment option for patients who do not respond well to existing therapies. METHODS: A randomized, open, parallel, single-center, phase I study was conducted to assess the pharmacokinetics, safety, and immunogenicity of single doses of QX002N injection administered intravenously (IV) or subcutaneously (SC) to healthy Chinese volunteers. Blood samples were collected at specified time intervals, and then serum concentrations of QX002N were analyzed by enzyme-linked immunosorbent assay. RESULTS: Pharmacokinetic analysis of the drug concentration-time data showed that the mean maximum observed serum QX002N concentration (Cmax) was 110 and 33.9 µg/ml, respectively. The average area under the drug concentration-time curves from 0 to the time of the last quantifiable concentration (AUClast) were 52,656 and 36,269 µg·h/ml, respectively and the average area under the drug concentration-time curves from 0 to infinity (AUCinf) were 54,867 and 38,194 µg·h/ml, respectively. The absolute bioavailability of QX002N after SC injection was 69.6%. CONCLUSIONS: Immunogenicity was assessed and all the subjects in this study were Anti-drug antibody (ADA)-negative, which means no subjects appeared to develop immunogenicity to QX002N. All the results testify to the safety of QX002N injection, which is satisfactory after IV or SC dosing in healthy subjects. TRIAL REGISTRATION: www.chinadrugtirals.org.cn , CTR20220430.

2.
Aging (Albany NY) ; 16(11): 9410-9436, 2024 Jun 06.
Article En | MEDLINE | ID: mdl-38848145

Although platinum-based chemotherapy is the frontline regimen for colorectal cancer (CRC), drug resistance remains a major challenge affecting its therapeutic efficiency. However, there is limited research on the correlation between chemotherapy resistance and lipid metabolism, including PIK3CA mutant tumors. In this present study, we found that PIK3CA-E545K mutation attenuated cell apoptosis and increased the cell viability of CRC with L-OHP treatment in vitro and in vivo. Mechanistically, PIK3CA-E545K mutation promoted the nuclear accumulation of SREBP1, which promoted the transcription of Apolipoprotein A5 (APOA5). APOA5 activated the PPARγ signaling pathway to alleviate reactive oxygen species (ROS) production following L-OHP treatment, which contributed to cell survival of CRC cells. Moreover, APOA5 overexpression enhanced the stemness-related traits of CRC cells. Increased APOA5 expression was associated with PIK3CA mutation in tumor specimens and poor response to first-line chemotherapy, which was an independent detrimental factor for chemotherapy sensitivity in CRC patients. Taken together, this study indicated that PIK3CA-E545K mutation promoted L-OHP resistance by upregulating APOA5 transcription in CRC, which could be a potent target for improving L-OHP chemotherapeutic efficiency. Our study shed light to improve chemotherapy sensitivity through nutrient management in CRC.


Apolipoprotein A-V , Class I Phosphatidylinositol 3-Kinases , Colorectal Neoplasms , Drug Resistance, Neoplasm , Mutation , Oxaliplatin , Reactive Oxygen Species , Humans , Colorectal Neoplasms/genetics , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/metabolism , Drug Resistance, Neoplasm/genetics , Apolipoprotein A-V/genetics , Apolipoprotein A-V/metabolism , Oxaliplatin/pharmacology , Oxaliplatin/therapeutic use , Reactive Oxygen Species/metabolism , Class I Phosphatidylinositol 3-Kinases/genetics , Class I Phosphatidylinositol 3-Kinases/metabolism , Animals , Cell Line, Tumor , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Mice , Male , Apoptosis/drug effects , Apoptosis/genetics , Sterol Regulatory Element Binding Protein 1/genetics , Sterol Regulatory Element Binding Protein 1/metabolism , Female , Gene Expression Regulation, Neoplastic/drug effects , Signal Transduction/drug effects
3.
Metabolism ; 157: 155954, 2024 Jun 13.
Article En | MEDLINE | ID: mdl-38878856

BACKGROUND: Metabolic diseases contribute significantly to premature mortality worldwide, with increasing burdens observed among the working-age population (WAP). This study assessed global, regional, and national trends in metabolic disorders and associated mortality over three decades in WAP. METHODS: Data from the Global Burden of Disease 2019 study were leveraged to assess global metabolism-associated mortality and six key metabolic risk factors in WAP from 1990-2019. An age-period-cohort model was employed to determine the overall percentage change in mortality. RESULTS: The 2019 global metabolic risk-related mortality rate in WAP rose significantly by 50.73%, while the age-standardized mortality rate declined by 21.5%. India, China, Indonesia, the USA, and the Russian Federation were the top contributing countries to mortality in WAP, accounting for 51.01% of the total. High systolic blood pressure (HSBP), high body mass index (HBMI), and high fasting plasma glucose (HFPG) were the top metabolic risk factors for the highest mortality rates. Adverse trends in HBMI-associated mortality were observed, particularly in lower sociodemographic index (SDI) regions. HFPG-related mortality declined globally but increased in older age groups in lower SDI countries. CONCLUSIONS: Despite a general decline in metabolic risk-related deaths in WAP, increasing HBMI- and HFPG-related mortality in lower SDI areas poses ongoing public health challenges. Developing nations should prioritize interventions addressing HBMI and HFPG to mitigate mortality risks in WAP.

4.
Mycologia ; : 1-11, 2024 Jun 07.
Article En | MEDLINE | ID: mdl-38848260

Fossil epifoliar fungi are valuable indicators of paleoenvironment and paleoecology. The Meliolaceae, members of which typically inhabit the surface of living plants as biotrophs or pathogens, is one of the largest groups of epifoliar fungi. In this study, we report a novel fossil species of Meliolinites Selkirk (fossil Meliolaceae), Meliolinites tengchongensis, on the lower epidermis of compressed fossil Rhodoleia (Hamamelidaceae) leaves from the Upper Pliocene Mangbang Formation of Tengchong, Yunnan, southwestern China. Meliolinites tengchongensis is characterized by web-like, superficial, brown to dark brown, septate, and branching mycelia bearing 2-celled appressoria and unicellular phialides. The fungal colonies also include ellipsoidal, 5-celled, 4-septate ascospores and dark brown perithecia with suborbicular outline and verrucose surface. The well-preserved vegetative and reproductive organs help us to explore the potential disease process of the new fossil species. Besides, the presence of fungal remains indicates that the fungal taxon might have maintained its host preference since at least the Late Pliocene. Furthermore, the occurrence of both fossil fungi and their host plants in Tengchong indicate a subtropical-tropical, warm, and humid climate during the Late Pliocene, whereas the distribution pattern of the fungi on the host leaves suggests that Rhodoleia may have been a part of the middle-upper canopies in the Tengchong Late Pliocene multilayered forest.

5.
J Control Release ; 371: 470-483, 2024 Jun 10.
Article En | MEDLINE | ID: mdl-38849094

Hypoimmunogenicity and the immunosuppressive microenvironment of ovarian cancer severely restrict the capability of immune-mediated tumor killing. Immunogenic cell death (ICD) introduces a theoretical principle for antitumor immunity by increasing antigen exposure and presentation. Despite recent research progress, the currently available ICD inducers are still very limited, and many of them can hardly induce sufficient ICD based on traditional endoplasmic reticulum (ER) stress. Accumulating evidence indicates that inducing mitochondrial stress usually shows a higher efficiency in evoking large-scale ICD than that via ER stress. Inspired by this, herein, a mitochondria-targeted polyprodrug nanoparticle (named Mito-CMPN) serves as a much superior ICD inducer, effectively inducing chemo-photodynamic therapy-caused mitochondrial stress in tumor cells. The rationally designed stimuli-responsive polyprodrugs, which can self-assemble into nanoparticles, were functionalized with rhodamine B for mitochondrial targeting, cisplatin and mitoxantrone (MTO) for synergistic chemo-immunotherapy, and MTO also serves as a photosensitizer for photodynamic immunotherapy. The effectiveness and robustness of Mito-CMPNs in reversing the immunosuppressive microenvironment is verified in both an ovarian cancer subcutaneous model and a high-grade serous ovarian cancer model. Our results support that the induction of abundant ICD by focused mitochondrial stress is a highly effective strategy to improve the therapeutic efficacy of immunosuppressive ovarian cancer.

6.
PLoS One ; 19(6): e0297215, 2024.
Article En | MEDLINE | ID: mdl-38875297

Dianthus barbatus linn. is widely used in gardens, mainly as flower beds and flower borders. The effects of different gradients of P on the growth and root morphology of Dianthus barbatus were studied to explore its morphological and physiological responses and adaptive strategies. Hence, this study provides a theoretical basis and practical guidance for D. barbatus production. Two soil substrates, namely loess and vegetable soil, and five phosphorus concentration gradients were set; no phosphorus application was used as the control. The morphology and physiology of D. barbatus were also investigated. Low-to-medium- and low-phosphorus treatments promoted the growth of D. barbatus in the above and underground parts of the plants grown on both substrates. Chlorophyll content, flower quantity, and acid phosphatase activity in the rhizosphere soil were significantly increased in the H1 and H2 treatments of loess and in the C4 treatment of vegetable soil. Thus, D. barbatus seems to reduce the damage caused by phosphorus stress by increasing chlorophyll content and root acid phosphatase activity. The latter was significantly higher in vegetable soil than in loess. Vegetable soil was more conducive to D. barbatus growth than loess.


Chlorophyll , Dianthus , Phosphorus , Plant Roots , Soil , Phosphorus/metabolism , Soil/chemistry , Chlorophyll/metabolism , Plant Roots/growth & development , Plant Roots/metabolism , Plant Roots/drug effects , Dianthus/growth & development , Dianthus/metabolism , Dianthus/physiology , Acid Phosphatase/metabolism , Flowers/metabolism , Flowers/growth & development , Rhizosphere
7.
Brain Behav ; 14(5): e3515, 2024 May.
Article En | MEDLINE | ID: mdl-38702895

INTRODUCTION: Maternal sleep deprivation (MSD), which induces inflammation and synaptic dysfunction in the hippocampus, has been associated with learning and memory impairment in offspring. Melatonin (Mel) has been shown to have anti-inflammatory, antioxidant, and neuroprotective function. However, the beneficial effect of Mel on MSD-induced cognitive impairment and its mechanisms are unknown. METHODS: In the present study, adult offspring suffered from MSD were injected with Mel (20 mg/kg) once a day during postnatal days 61-88. The cognitive function was evaluated by the Morris water maze test. Levels of proinflammatory cytokines were examined by enzyme-linked immunosorbent assay. The mRNA and protein levels of synaptic plasticity associated proteins were examined using reverse transcription-polymerase chain reaction and western blotting. RESULTS: The results showed that MSD impaired learning and memory in the offspring mice. MSD increased the levels of interleukin (IL)-1creIL-6, and tumor necrosis factor-α and decreased the expression levels of brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density protein-95, and synaptophysin in the hippocampus. Furthermore, Mel attenuated cognitive impairment and restored markers of inflammation and synaptic plasticity to control levels. CONCLUSIONS: These findings indicated that Mel could ameliorate learning and memory impairment induced by MSD, and these beneficial effects were related to improvement in inflammation and synaptic dysfunction.


Hippocampus , Melatonin , Memory Disorders , Neuronal Plasticity , Sleep Deprivation , Animals , Melatonin/pharmacology , Melatonin/administration & dosage , Sleep Deprivation/complications , Sleep Deprivation/drug therapy , Sleep Deprivation/physiopathology , Mice , Male , Hippocampus/metabolism , Hippocampus/drug effects , Female , Memory Disorders/drug therapy , Memory Disorders/etiology , Memory Disorders/physiopathology , Neuronal Plasticity/drug effects , Inflammation/drug therapy , Inflammation/metabolism , Pregnancy , Maternal Deprivation , Cognitive Dysfunction/etiology , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/physiopathology , Prenatal Exposure Delayed Effects/metabolism , Prenatal Exposure Delayed Effects/physiopathology , Brain-Derived Neurotrophic Factor/metabolism , Neuroinflammatory Diseases/drug therapy
8.
Int J Nanomedicine ; 19: 4253-4261, 2024.
Article En | MEDLINE | ID: mdl-38766662

Purpose: Recently, Single-atom-loaded carbon-based material is a new environmentally friendly and stable photothermal antibacterial nanomaterial. It is still a great challenge to achieve single-atom loading on carbon materials. Materials and Methods: Herein, We doped single-atom Ag into ZIF-8-derived porous carbon to obtain Ag-doped ZIF-8-derived porous carbon(AgSA-ZDPC). The as-prepared samples were characterized by XRD, XPS, FESEM, EDX, TEM, and HAADF-STEM which confirmed that the single-atom Ag successfully doped into the porous carbon. Further, the photothermal properties and antimicrobial activity of AgSA-ZDPC have been tested. Results: The results showed that the temperature increased by 30 °C after near-infrared light irradiation(1 W/cm2) for 5 min which was better than ZIF-8-derived porous carbon(ZDPC). It also exhibits excellent photothermal stability after the laser was switched on and off 5 times. When the AgSA-ZDPC concentration was greater than 50 µg/mL and the near-infrared irradiation was performed for 5 min, the growth inhibition of S. aureus and E. coli was almost 100%. Conclusion: This work provides a simple method for the preparation of single-atom Ag-doped microporous carbon which has potential antibacterial application.


Anti-Bacterial Agents , Carbon , Escherichia coli , Silver , Staphylococcus aureus , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Silver/chemistry , Silver/pharmacology , Porosity , Escherichia coli/drug effects , Staphylococcus aureus/drug effects , Carbon/chemistry , Carbon/pharmacology , Infrared Rays , Microbial Sensitivity Tests , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Zeolites/chemistry , Zeolites/pharmacology , Imidazoles
9.
Kaohsiung J Med Sci ; 2024 May 27.
Article En | MEDLINE | ID: mdl-38801488

Bladder cancer (BC) poses high morbidity and mortality, with urinary exosomal microRNA (miR)-21 showing potential value in its diagnosis and prognosis, and we probed its specific role. We prospectively selected 116 BC patients and 116 healthy volunteers as the BC and control groups, respectively. BC urinary exosomal miR-146a-5p, miR-93-5p, miR-663b, miR-21, and miR-4454 relative expression levels were assessed. The correlations between clinical indexes and urinary exosomal miR-21, prognostic value of miR-21, and diagnostic value of the five candidate miRNAs, urine cytology, and miRNA joint diagnostic panel for BC and urinary exosomal miR-21, miR-4454, and urine cytology for Ta-T1 and T2-T4 stage BC were analyzed. Urinary exosomal miR-146a-5p, miR-93-5p, miR-663b, miR-21, and miR-4454 were highly expressed in BC patients. miR-146a-5p, miR-93-5p, miR-663b, miR-21, miR-4454, miRNA combined diagnostic panel, and urine cytology had certain diagnostic value for BC, with miR-21, miR-4454, and miRNA co-diagnostic panel showing the highest diagnostic value. Collectively, urinary exosomal miR-21 was closely related to Tumor-Node-Metastasis staging and grading in BC patients. Urinary exosomal miR-21 had high diagnostic value for BC and Ta-T1 and T2-T4 stage BC, and had high predictive value for BC poor prognosis, providing an effective indicator for the occurrence, development, and prognostic assessment of BC.

10.
Front Psychiatry ; 15: 1360305, 2024.
Article En | MEDLINE | ID: mdl-38803679

Objectives: To examine serum concentrations of neurotensin, pannexin-1 and sestrin-2, and their correlations with subjective and objective sleep quality and cognitive function in the patients with chronic insomnia disorder (CID). Methods: Sixty-five CID patients were enrolled continuously and fifty-six good sleepers in the same period were served as healthy controls (HCs). Serum levels of neurotensin, pannexin-1 and sestrin-2 were measured by enzyme-linked immunosorbent assays. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and polysomnography, and mood was evaluated by 17-item Hamilton Depression Rating Scale. General cognitive function was assessed with the Chinese-Beijing Version of Montreal Cognitive Assessment and spatial memory was evaluated by Blue Velvet Arena Test (BVAT). Results: Relative to the HCs, the CID sufferers had higher levels of neurotensin (t=5.210, p<0.001) and pannexin-1 (Z=-4.169, p<0.001), and lower level of sestrin-2 (Z=-2.438, p=0.015). In terms of objective sleep measures, pannexin-1 was positively associated with total sleep time (r=0.562, p=0.002) and sleep efficiency (r=0.588, p=0.001), and negatively with wake time after sleep onset (r=-0.590, p=0.001) and wake time (r=-0.590, p=0.001); sestrin-2 was positively associated with percentage of rapid eye movement sleep (r=0.442, p=0.016) and negatively with non-rapid eye movement sleep stage 2 in the percentage (r=-0.394, p=0.034). Adjusted for sex, age and HAMD, pannexin-1 was still associated with the above objective sleep measures, but sestrin-2 was only negatively with wake time (r=-0.446, p=0.022). However, these biomarkers showed no significant correlations with subjective sleep quality (PSQI score). Serum concentrations of neurotensin and pannexin-1 were positively associated with the mean erroneous distance in the BVAT. Adjusted for sex, age and depression, neurotensin was negatively associated with MoCA score (r=-0.257, p=0.044), pannexin-1 was positively associated with the mean erroneous distance in the BVAT (r=0.270, p=0.033). Conclusions: The CID patients had increased neurotensin and pannexin-1 and decreased sestrin-2 in the serum levels, indicating neuron dysfunction, which could be related to poor sleep quality and cognitive dysfunction measured objectively.

11.
J Clin Psychol ; 2024 May 23.
Article En | MEDLINE | ID: mdl-38781606

OBJECTIVES: Previous research suggests potential moderating roles of dispositional mindfulness and body image flexibility in the association between body dissatisfaction and disordered eating. However, relevant research is mainly conducted on adult women from Western countries, and limited evidence exists for adolescent samples, especially from non-Western contexts (e.g., China). Thus, this study aimed to examine the moderating roles of dispositional mindfulness and body image flexibility in the relationship between body dissatisfaction and disordered eating in Chinese adolescents. METHOD: We recruited 545 Chinese adolescents (53.9% boys, aged 12-16 years) who completed measures of body dissatisfaction, dispositional mindfulness, body image flexibility, and disordered eating. Moderation analyses were examined with PROCESS macro on SPSS. RESULTS: In separate models, both higher dispositional mindfulness and body image flexibility weakened relationships between body dissatisfaction and disordered eating. However, when both dispositional mindfulness and body image flexibility were entered into the same moderation model, only body image flexibility showed a significant moderating effect. DISCUSSION: Both dispositional mindfulness and body image flexibility may weaken the association between body dissatisfaction and disordered eating in adolescents. However, body image flexibility might have a stronger effect than dispositional mindfulness. These findings suggest that interventions aimed at reducing body dissatisfaction to prevent disordered eating in adolescents may pay more attention to adolescents' body image flexibility.

12.
Plants (Basel) ; 13(9)2024 May 06.
Article En | MEDLINE | ID: mdl-38732494

Microplastic might affect the crop yield, nitrogen (N) use efficiency and reactive N losses from agricultural soil systems. However, evaluation of these effects in infertile soil planted with different rice cultivars is lacking. We conducted a soil column experiment to determine the influence of a typical microplastic polyethylene (PE) input into an infertile soil with 270 kg N ha-1 and planted with two rice cultivars, i.e., a common rice Nangeng 5055 (NG) and a hybrid rice Jiafengyou 6 (JFY). The results showed that JFY produced a significantly (p < 0.05) greater grain yield than NG (61.6-66.2 vs. 48.2-52.5 g pot-1) but was not influenced by PE. Overall, PE hardly changed the N use efficiency of NG and JFY. Unexpectedly, PE significantly (p < 0.05) increased the total amino acid content of NG. Compared with JFY, NG volatilized significantly (p < 0.05) more ammonia (NH3) (0.84-0.92 vs. 0.64-0.67 g N pot-1) but emitted equal nitrous oxide (N2O). PE exerted no effect on either NH3 volatilization or the N2O emission flux pattern and cumulative losses of the rice growth cycle, whether with NG or JFY. Some properties of tested soils changed after planting with different rice cultivars and incorporating with microplastic. In conclusion, the rice production, N use efficiency, NH3 volatilization and N2O emission from the N-fertilized infertile soil were pronouncedly influenced by the rice cultivar, but not the PE. However, PE influenced the grain quality of common rice and some properties of tested soils with both rice cultivars.

13.
J Control Release ; 370: 677-690, 2024 Jun.
Article En | MEDLINE | ID: mdl-38740093

The low oxidation level and immunosuppressive microenvironment within hypoxic tumor tissue are critical factors contributing to the inefficacy of various anti-tumor strategies. Herein, we have designed a novel intravenous injection nanoplatform to conduct electro-immunotherapy, based on phospholipid-modified PtPd nanocrystals loaded with the immunoregulator IPI549 (LP@Pt-Pd@IPI549 nanoparticles, LPPI). LPPI responds to reactive oxygen species (ROS), triggering a cascade of therapeutic effects that overcome hypoxia-related resistance and effectively eradicate hypoxic tumors. Firstly, under electric field exposure, LPPI relied on water rather than oxygen to generate abundant ROS under hypoxic conditions for tumor electrodynamic therapy (EDT). Moreover, the generated ROS further induced the disintegration of the outer phospholipid membrane of LPPI, leading to the release of the immunoregulator and inhibition of myeloid-derived suppressor cells (MDSCs), triggering cascade immune responses. Additionally, the immunomodulatory effects of IPI549, in synergy with the immunogenic cell death (ICD) induced by EDT, reversed the immunosuppressive microenvironment contributing to tumor resistance. In summary, EDT transiently killed tumor cells while simultaneously generating antigen release, instigating an adaptive immune response for electro-immunotherapy, resulting in a potent and long-lasting tumor inhibition effect.


Immunotherapy , Reactive Oxygen Species , Animals , Reactive Oxygen Species/metabolism , Immunotherapy/methods , Cell Line, Tumor , Humans , Tumor Microenvironment/drug effects , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Mice, Inbred C57BL , Platinum/chemistry , Mice , Female , Neoplasms/therapy , Neoplasms/immunology , Oxygen/administration & dosage , Palladium/chemistry , Palladium/administration & dosage , Mice, Inbred BALB C , Myeloid-Derived Suppressor Cells/drug effects , Myeloid-Derived Suppressor Cells/immunology , Phospholipids/chemistry , Phospholipids/administration & dosage , Metal Nanoparticles/administration & dosage , Metal Nanoparticles/chemistry
14.
Acta Pharmacol Sin ; 2024 Apr 26.
Article En | MEDLINE | ID: mdl-38671193

Despite the widespread prevalence and important medical impact of insomnia, effective agents with few side effects are lacking in clinics. This is most likely due to relatively poor understanding of the etiology and pathophysiology of insomnia, and the lack of appropriate animal models for screening new compounds. As the main homeostatic, circadian, and neurochemical modulations of sleep remain essentially similar between humans and rodents, rodent models are often used to elucidate the mechanisms of insomnia and to develop novel therapeutic targets. In this article, we focus on several rodent models of insomnia induced by stress, diseases, drugs, disruption of the circadian clock, and other means such as genetic manipulation of specific neuronal activity, respectively, which could be used to screen for novel hypnotics. Moreover, important advantages and constraints of some animal models are discussed. Finally, this review highlights that the rodent models of insomnia may play a crucial role in novel drug development to optimize the management of insomnia.

15.
Chin J Integr Med ; 30(6): 565-576, 2024 Jun.
Article En | MEDLINE | ID: mdl-38565799

Intestinal macrophages play crucial roles in both intestinal inflammation and immune homeostasis. They can adopt two distinct phenotypes, primarily determined by environmental cues. These phenotypes encompass the classically activated pro-inflammatory M1 phenotype, as well as the alternatively activated anti-inflammatory M2 phenotype. In regular conditions, intestinal macrophages serve to shield the gut from inflammatory harm. However, when a combination of genetic and environmental elements influences the polarization of these macrophages, it can result in an M1/M2 macrophage activation imbalance, subsequently leading to a loss of control over intestinal inflammation. This shift transforms normal inflammatory responses into pathological damage within the intestines. In patients with ulcerative colitis-associated colorectal cancer (UC-CRC), disorders related to intestinal inflammation are closely correlated with an imbalance in the polarization of intestinal M1/M2 macrophages. Therefore, reinstating the equilibrium in M1/M2 macrophage polarization could potentially serve as an effective approach to the prevention and treatment of UC-CRC. This paper aims to scrutinize the clinical evidence regarding Chinese medicine (CM) in the treatment of UC-CRC, the pivotal role of macrophage polarization in UC-CRC pathogenesis, and the potential mechanisms through which CM regulates macrophage polarization to address UC-CRC. Our objective is to offer fresh perspectives for clinical application, fundamental research, and pharmaceutical advancement in UC-CRC.


Colitis-Associated Neoplasms , Disease Progression , Macrophages , Humans , Macrophages/pathology , Colitis-Associated Neoplasms/pathology , Colitis-Associated Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Animals , Colitis, Ulcerative/pathology , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/complications
16.
Brain Behav ; 14(5): e3508, 2024 May.
Article En | MEDLINE | ID: mdl-38688894

BACKGROUND: The inflammation and synaptic dysfunction induced by mitochondrial dysfunction play essential roles in the learning and memory impairment associated with sleep dysfunction. Elamipretide (SS-31), a novel mitochondrion-targeted antioxidant, was proven to improve mitochondrial dysfunction, the inflammatory response, synaptic dysfunction, and cognitive impairment in models of cerebral ischemia, sepsis, and type 2 diabetes. However, the potential for SS-31 to improve the cognitive impairment induced by chronic sleep deprivation (CSD) and its underlying mechanisms is unknown. METHODS: Adult c57BL/6J mice were subjected to CSD for 21 days using an activity wheel accompanied by daily intraperitoneal injection of SS-31 (5 mg/kg). The novel object recognition and Morris water maze test were used to evaluate hippocampus-dependent cognitive function. Western blotting and reverse transcription-quantitative polymerase chain reaction assays were used to determine the effects of CSD and SS-31 on markers of mitochondria, inflammation response, and synaptic function. Enzyme-linked immunosorbent assays were used to examine the levels of proinflammatory cytokines. RESULTS: SS-31 could improve the cognitive impairment induced by CSD. In particular, SS-31 treatment restored the CSD-induced decrease in sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor γ coactivator alpha levels and the increase in levels nuclear factor kappa-B and inflammatory cytokines, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha. Furthermore, SS-31 significantly increased the levels of brain-derived neurotrophic factor, postsynaptic density protein-95, and synaptophysin in CSD mice. CONCLUSION: Taken together, these results suggest that SS-31 could improve CSD-induced mitochondrial biogenesis dysfunction, inflammatory response, synaptic dysfunction, and cognitive impairment by increasing SIRT1 expression levels.


Antioxidants , Mice, Inbred C57BL , Mitochondria , Oligopeptides , Sleep Deprivation , Animals , Mice , Sleep Deprivation/drug therapy , Sleep Deprivation/complications , Sleep Deprivation/metabolism , Oligopeptides/pharmacology , Oligopeptides/administration & dosage , Male , Mitochondria/drug effects , Mitochondria/metabolism , Antioxidants/pharmacology , Hippocampus/metabolism , Hippocampus/drug effects , Memory Disorders/drug therapy , Memory Disorders/etiology , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/etiology , Sirtuin 1/metabolism , Disease Models, Animal
18.
Water Res ; 256: 121607, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38640568

This work investigates the physicochemical characteristics of grease-trap wastewater discharged from a large community market. It proposes potential mechanisms of fat, oil, and grease (FOG) solid formation, separation, and accumulation inside grease traps. Sixty-four samples, i.e., the floated scum, suspended solid-liquid wastewater, and settled sludge, were collected from the grease-trap inlet and outlet chambers. A lower pH of 5-6 at 25-29 °C inside the grease trap than those reported under the sewer conditions (pH 6-7) was revealed. A significant difference in solid and dissolved constituents was also discovered between the inlet and outlet chambers, indicating that the baffle wall could affect the separation mechanism. The sludge samples had 1.5 times higher total solids (TS) than the scum samples, i.e., 0.225 vs. 0.149 g g-1 TS, revealing that the sludge amount impacted more significantly the grease trap capacity and operation and maintenance. In contrast, the scum samples had 1.4 times higher volatile solids (VS) than the sludge samples, i.e., 0.134 vs. 0.096 g g-1 VS, matching with the 64.2 vs. 29.7% of carbon content from CHN analysis. About 2/3 of the free fatty acids (FFAs) with palmitic acids were the primary saturated FFAs, while the remaining 1/3 of unsaturated FFAs were found in the solid and liquid samples. Although up to 0.511 g g-1 FOG can be extracted from the scum samples, none from the sludge samples. More diverse minerals/metals other than Na, Cl, and Ca were found in the sludge samples than in the scum samples. Grease-trap FOG solids and open drain samples exhibited similar physicochemical properties to those reported in the literature. Four potential mechanisms (crystallization, emulsification, saponification, and baffling) were presented. This work offers insights into the physicochemical properties of grease-trap wastewater that can help explore its FOG solid formation, separation, and accumulation mechanisms inside a grease trap.


Sewage , Waste Disposal, Fluid , Wastewater , Wastewater/chemistry , Sewage/chemistry
19.
Sleep Med ; 117: 162-168, 2024 May.
Article En | MEDLINE | ID: mdl-38547593

BACKGROUND AND OBJECTIVE: Rumination, a common factor of chronic insomnia disorder (CID) caused by cognitive-emotional arousal, is associated with an increased amount of rapid eye movement (REM) sleep. However, the specific subtypes, such as phasic REM and tonic REM, that contribute to the increased REM sleep have not been reported. This study aimed to determine the association between rumination and different REM sleep subtypes in patients with CID. METHODS: This study enrolled 35 patients with CID and 27 age- and sex-matched healthy controls. The Immersion-Rumination Questionnaire evaluated participants' rumination, and the Insomnia Severity Index was used to assess insomnia severity. Finally, polysomnography was used to monitor objective sleep quality and quantification of different types of REM. RESULTS: The CID patients had higher rumination scores than the healthy controls. They had a shorter REM sleep duration, less phasic REM, a lower percentage of phasic REM time, and a higher percentage of tonic REM time. Spectral analysis revealed that the patients affected by insomnia had higher ß power during REM sleep, higher ß and σ power during phasic REM sleep, and higher ß, and γ power during tonic REM sleep. Partial correlation analysis showed that rumination in the CID patients correlated negatively with the duration of phasic REM sleep. Additionally, rumination correlated negatively with δ power in REM sleep and positively with ß power in REM sleep, tonic REM sleep, phasic REM sleep, N3and N2 sleep in the patients with CID. CONCLUSION: The CID patients had stronger rumination, reduced total and phasic REM sleep, and the stronger rumination was, the shorter phasic REM was and the higher fast (ß) wave power in REM sleep.


REM Sleep Behavior Disorder , Sleep Initiation and Maintenance Disorders , Humans , Sleep, REM , Sleep Initiation and Maintenance Disorders/complications , Polysomnography , Arousal , REM Sleep Behavior Disorder/complications
20.
Sleep Med ; 117: 177-183, 2024 May.
Article En | MEDLINE | ID: mdl-38554533

OBJECTIVES: To explore the relationship between nocturnal levels of stress-related hormones and different sleep-wake states in chronic insomnia disorder (CID) patients. METHODS: Thirty-three CID patients and 34 good sleepers were enrolled and completed assessment of sleep log, Pittsburgh Sleep Quality Index and Insomnia Severity Index. During a-overnight polysomnography monitoring, the patients' vein bleeds were continually collected at different time points (pre-sleep, deep-sleep, 5-min or 30-min waking, and morning waking-up). The control subjects' bleeds were collected only at 22:00 and morning waking-up. The serum hormones were detected using enzyme-linked immunosorbent assay. RESULTS: Compared with at pre-sleep, the level of cortisol was significantly higher at morning waking-up respectively in two-group subjects (Ps < 0.001), with insignificant inter-group differences in cortisol, corticotropin releasing hormone and copeptin at the two time-points. In the patients, the nocturnal secretion curves of three hormones were similar, with the highest concentration at morning waking-up, followed by 30-min waking, 5-min waking, pre-sleep, and deep-sleep. The patients' cortisol (Z = 79.192, P < 0.001) and copeptin (Z = 12.333, P = 0.015) levels were statistically different at different time-points, with higher cortisol at morning waking-up relative to deep-sleep, pre-sleep and 5-min waking (Ps < 0.05), and at 30-min waking relative to deep-sleep and pre-sleep (Ps < 0.05), and higher copeptin at morning waking-up relative to deep-sleep (P < 0.05). CONCLUSIONS: In CID, the nocturnal wakes were instantaneously accompanied by high level, and deep sleep was accompanied by the lowest levels, of stress-related hormones, especially in cortisol, supporting the insomniac hypothesis of increased nocturnal pulse-release of cortisol.


Sleep Initiation and Maintenance Disorders , Humans , Pilot Projects , Hydrocortisone , Sleep , Polysomnography
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