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2.
Lipids Health Dis ; 23(1): 282, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39232759

ABSTRACT

OBJECTIVE: This study aimed to reveal the role and mechanism of MG-132 in delaying hyperlipidemia-induced senescence of vascular smooth muscle cells (VSMCs). METHODS: Immunohistochemistry and hematoxylin-eosin staining confirmed the therapeutic effect of MG-132 on arterial senescence in vivo and its possible mechanism. Subsequently, VSMCs were treated with sodium palmitate (PA), an activator (Recilisib) or an inhibitor (Pictilisib) to activate or inhibit PI3K, and CCK-8 and EdU staining, wound healing assays, Transwell cell migration assays, autophagy staining assays, reactive oxygen species assays, senescence-associated ß-galactosidase staining, and Western blotting were performed to determine the molecular mechanism by which MG-132 inhibits VSMC senescence. Validation of the interaction between MG-132 and PI3K using molecular docking. RESULTS: Increased expression of p-PI3K, a key protein of the autophagy regulatory system, and decreased expression of the autophagy-associated proteins Beclin 1 and ULK1 were observed in the aortas of C57BL/6J mice fed a high-fat diet (HFD), and autophagy was inhibited in aortic smooth muscle. MG-132 inhibits atherosclerosis by activating autophagy in VSMCs to counteract PA-induced cell proliferation, migration, oxidative stress, and senescence, thereby inhibiting VSMC senescence in the aorta. This process is achieved through the PI3K/AKT/mTOR signaling pathway. CONCLUSION: MG-132 activates autophagy by inhibiting the PI3K/AKT/mTOR pathway, thereby inhibiting palmitate-induced proliferation, migration, and oxidative stress in vascular smooth muscle cells and suppressing their senescence.


Subject(s)
Autophagy , Cellular Senescence , Leupeptins , Muscle, Smooth, Vascular , Myocytes, Smooth Muscle , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Signal Transduction , TOR Serine-Threonine Kinases , Autophagy/drug effects , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/cytology , TOR Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Animals , Cellular Senescence/drug effects , Humans , Phosphatidylinositol 3-Kinases/metabolism , Mice , Signal Transduction/drug effects , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/metabolism , Leupeptins/pharmacology , Male , Mice, Inbred C57BL , Palmitic Acid/pharmacology , Cell Proliferation/drug effects , Cell Movement/drug effects , Diet, High-Fat/adverse effects
4.
Clin Lab ; 70(9)2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39257108

ABSTRACT

BACKGROUND: There have been only few reports on Rhupus syndrome with severe visceral involvement. Moreover, there was little consensus regarding its treatment. Belimumab is one of the options for treating this disease. For patients with clinical symptoms and elevated levels of anti CCP antibodies and anti-double stranded DNA antibodies, and it suggests Rhupus syndrome. After effective treatment, the decrease in levels of anti CCP antibodies and anti-double stranded DNA (ds-DNA) antibodies can effectively delay the progression of the disease and protect target organs. METHODS: We used a chemiluminescence instrument, (Yahuilong; Shenzhen, China), to measure the changes in CCP and dsDNA before and after treatment. RESULTS: Prior to treatment, the patient presented with symptoms of rheumatoid arthritis and systemic lupus erythematosus. Her laboratory tests showed dsDNA (214 IU/mL) and CCP level of ˃ 3,000 U/mL. After treatment with belimumab, the clinical symptoms were significantly relieved, and the patient's CCP IgG level decreased to 263.5 U/mL. A blood test found that her anti-dsDNA was negative. CONCLUSIONS: CCP and dsDNA can serve as indicators for the diagnosis and treatment of Rhupus syndrome.


Subject(s)
Antibodies, Antinuclear , Antibodies, Monoclonal, Humanized , DNA , Humans , Female , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Antinuclear/blood , Antibodies, Antinuclear/immunology , DNA/immunology , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/blood , Middle Aged , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/blood , Immunosuppressive Agents/therapeutic use , Treatment Outcome , Autoantibodies/blood , Autoantibodies/immunology , Adult , Biomarkers/blood
5.
Health Qual Life Outcomes ; 22(1): 73, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39227972

ABSTRACT

BACKGROUND: Computerized adaptive testing (CAT) is an effective way to reduce time, repetitious redundancy, and respond burden, and has been used to measure outcomes in many diseases. This study aimed to develop and validate a comprehensive disease-specific CAT for chronic obstructive pulmonary disease (COPD) patient-reported outcome measurement. METHODS: The discrimination and difficulty of the items from the modified patient-reported outcome scale for COPD (mCOPD-PRO) were analyzed using item response theory. Then the initial item, item selection method, ability estimation method, and stopping criteria were further set based on Concerto platform to form the CAT. Finally, the reliability and validity were validated. RESULTS: The item discrimination ranged from 1.05 to 2.71, and the item difficulty ranged from - 3.08 to 3.65. The measurement reliability of the CAT ranged from 0.910 to 0.922 using random method, while that ranged from 0.910 to 0.924 using maximum Fisher information (MFI) method. The content validity was good. The correlation coefficient between theta of the CAT and COPD assessment test and modified Medical Research Council dyspnea scale scores using random method was 0.628 and 0.540 (P < 0.001; P < 0.001) respectively, while that using MFI method was 0.347 and 0.328 (P = 0.007; P = 0.010) respectively. About 11 items (reducing by 59.3%) on average were tested using random method, while about seven items (reducing by 74.1%) on average using MFI method. The correlation coefficient between theta of the CAT and mCOPD-PRO total scores using random method was 0.919 (P < 0.001), while that using MFI method was 0.760 (P < 0.001). CONCLUSIONS: The comprehensive disease-specific CAT for COPD patient-reported outcome measurement is well developed with good psychometric properties, which can provide an efficient, accurate, and user-friendly measurement for patient-reported outcome of COPD.


Subject(s)
Patient Reported Outcome Measures , Psychometrics , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/psychology , Male , Female , Reproducibility of Results , Middle Aged , Aged , Surveys and Questionnaires/standards , Quality of Life
6.
Article in English | MEDLINE | ID: mdl-39236286

ABSTRACT

The role of circRNAs in sepsis-induced lung injury is not clear. This study investigated the role and molecular mechanism of a novel circRNA in sepsis-induced lung injury and explored its prognostic value in sepsis patients. In this study, aberrant circRNA expression profiling in lung tissues from mice with sepsis-induced lung injury was analyzed using high-throughput sequencing. CircRNA-Cacna1d was verified by quantitative real-time polymerase chain reaction, and its biological function in sepsis-induced lung injury was validated in vitro and in vivo. The interactions among circRNA-Cacna1d, miRNAs, and their downstream genes were verified. Furthermore, the clinical value of circRNA-Cacna1d in peripheral blood from sepsis patients was also evaluated. We found that circRNA-Cacna1d expression was significantly increased in lung tissues of sepsis mice and microvascular endothelial cells after lipopolysaccharide (LPS) challenge. CircRNA-Cacna1d knockdown alleviated inflammatory response and ameliorated the permeability of vascular endothelium, thereby mitigating sepsis-induced lung injury and significantly improving the survival rate of sepsis mice. Mechanistically, circRNA-Cacna1d directly interacted with miRNA-185-5p and functioned as a miRNA sponge to regulate the RhoA/ROCK1 signaling pathway. The expression level of circRNA-Cacna1d in patients with early sepsis was significantly higher than that in the healthy controls. Higher levels of circRNA-Cacna1d in sepsis patients were associated with increased disease severity and poorer outcomes. In conclusions, circRNA-Cacna1d may play a role in sepsis-induced lung injury by regulating the RhoA/ROCK1 axis by acting as miRNA-185-5p sponge. CircRNA-Cacna1d is a potential therapeutic target for sepsis-induced lung injury and a prognostic biomarker in sepsis.

7.
Ecol Evol ; 14(9): e70268, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39263460

ABSTRACT

Macropsini is a tribe of Eurymelinae in the family Cicadellidae that is widely distributed worldwide. Still, its taxonomic status has been unstable, and the classification of certain clades at the genus level has been controversial. The aim of this study is to address the patterns and processes that explain the structure and the evolution of the mitogenomes of Macropsini, while contributing to the resolution of systematic issues involving five of their genera. To this task, the mitogenomes of 26 species of the tribe were sequenced and characterized, and their phylogenetic relationships were reconstructed. The results revealed that the nucleotide composition of mitochondrial genes in these 26 species was significantly skewed toward A and T. Codons ending with T or A in relative synonymous codon usage were significantly more prevalent than those ending with C or G. The parity plot, neutrality plot, and correspondence analysis revealed that mutation and selective pressure affect codon usage patterns. In the phylogenetic relationships of the Macropsini, the monophyly of Pedionis and Macropsis was well-supported. Meanwhile, Oncopsis revealed paraphyletic regarding Pediopsoides. In conclusion, this research not only contributes the valuable data to the understanding of the mitogenome of the Macropsini but also provides a reference for future investigations on codon usage patterns, potential adaptive evolution, and the phylogeny of the mitogenome within the subfamily Eurymelinae.

8.
Semin Arthritis Rheum ; 68: 152537, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39146916

ABSTRACT

OBJECTIVE: Primary Sjögren's Syndrome (pSS) is a complex autoimmune disorder characterized by diverse clinical manifestations yet lacking effective therapeutic strategies currently. This study aims to gain a thorough understanding of the clinical landscape of pSS and further delineate its clinical subtypes, thereby enabling the efficient management for pSS. METHODS: We conducted a cross-sectional observational study of 1318 pSS patients. The pSS patients were categorized and compared based on gender, anti-SSA antibodies, and labial salivary gland biopsies (LGSB). Unsupervised clustering analysis was employed to identify pSS subtypes using systemic involvement among patients. Furthermore, we assessed clinical and biological variances among these subtypes. RESULTS: Through group comparisons, we observed more pronounced extraglandular manifestations among male patients, SSA-negative group, and those with positive LGSB results. Based on systemic involvement, pSS patients were categorized into four groups. C1 exhibited minimal systemic involvement, lacking hematologic or serologic manifestations, with the lowest ESSDAI scores. C2 presented with serologic changes in all patients, partial joint involvement, and no hematologic systemic manifestations. C3 lacked joint involvement but all members displayed hematologic systemic involvement, with higher rates of renal, cutaneous, and systemic manifestations. C4 encompassed patients with joint and hematologic involvement, displaying the highest ESSDAI scores. The positivity rates of antibodies, immunological parameters, and inflammatory markers exhibited significant differences among the groups. Furthermore, notable variances were observed in the expression of peripheral blood transcriptomic modules among these groups. CONCLUSION: In this cohort study, we summarized the clinical characteristics of Chinese patients with pSS and identified four distinct subgroups of pSS based on systemic involvement, revealing clinical and molecular disparities that unveil distinct pathobiological endotypes. Our findings hold significant implications for clinical management.


Subject(s)
Sjogren's Syndrome , Humans , Sjogren's Syndrome/immunology , Sjogren's Syndrome/blood , Male , Female , Cross-Sectional Studies , Middle Aged , Adult , Aged , Antibodies, Antinuclear/blood , Antibodies, Antinuclear/immunology , Salivary Glands/pathology , Salivary Glands/immunology
10.
Sci China Life Sci ; 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39187660

ABSTRACT

Switching from mitotic spermatogonia to meiotic spermatocytes is critical to producing haploid sperms during male germ cell differentiation. However, the underlying mechanisms of this switch remain largely unexplored. In Drosophila melanogaster, the gene RpL38 encodes the ribosomal protein L38, one component of the 60S subunit of ribosomes. We found that its depletion in spermatogonia severely diminished the production of mature sperms and thus led to the infertility of male flies. By examining the germ cell differentiation in testes, we found that RpL38-knockdown blocked the transition from spermatogonia to spermatocytes and accumulated spermatogonia in the testis. To understand the intrinsic reason for this blockage, we conducted proteomic analysis for these spermatogonia populations. Differing from the control spermatogonia, the accumulated spermatogonia in RpL38-knockdown testes already expressed many spermatocyte markers but lacked many meiosis-related proteins, suggesting that spermatogonia need to prepare some important proteins for meiosis to complete their switch into spermatocytes. Mechanistically, we found that the expression of bag of marbles (bam), a crucial determinant in the transition from spermatogonia to spermatocytes, was inhibited at both the mRNA and protein levels upon RpL38 depletion. We also confirmed that the bam loss phenocopied RpL38 RNAi in the testis phenotype and transcriptomic profiling. Strikingly, overexpressing bam was able to fully rescue the testis abnormality and infertility of RpL38-knockdown flies, indicating that bam is the key effector downstream of RpL38 to regulate spermatogonia differentiation. Overall, our data suggested that germ cells start to prepare meiosis-related proteins as early as the spermatogonial stage, and RpL38 in spermatogonia is required to regulate their transition toward spermatocytes in a bam-dependent manner, providing new knowledge for our understanding of the transition process from spermatogonia to spermatocytes in Drosophila spermatogenesis.

11.
Microbiol Spectr ; : e0126524, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39162496

ABSTRACT

Myxomycetes are fungus-like organisms that play a significant role in ecological processes, however, their taxonomic diversity and distribution in China are poorly understood. Diderma is an important genus within the Class Myxogastria that has received little attention in China. This study provides new insights into the geographic range of Diderma species in China and identifies previously unreported and newly recorded species. Our results reveal that the geographic distribution of Diderma species in China is more diverse than previously thought, with four previously unreported species found in Liaoning, Hubei, Sichuan, and Gansu provinces. In addition, we describe five new Diderma species that are distinct from previously known species, namely Diderma annuliferum, Diderma gansuense, Diderma roseum, Diderma jilinense, and Diderma flexocapillitium. We identified these species using a combination of morphological characterization, DNA sequencing, and phylogenetic analysis. Our findings have important implications for understanding Myxomycete biodiversity in China and can inform future research on the ecology, biogeography, and evolution of these fascinating organisms. Specifically, our study highlights the need for continued exploration of underrepresented areas to gain a more comprehensive understanding of the diversity and distribution of Myxomycetes in China. IMPORTANCE: The discovery of five new Diderma species and the revelation of their diverse distribution expand our understanding of Myxomycete diversity and provide a foundation for future studies on the ecology and biogeography of these organisms. These findings contribute to our knowledge of microbial diversity and have practical implications for conserving underrepresented areas and maintaining healthy ecosystems.

12.
Expert Rev Mol Diagn ; 24(8): 703-713, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39158206

ABSTRACT

INTRODUCTION: Diabetic microvascular complications such as retinopathy, nephropathy, and neuropathy are primary causes of blindness, terminal renal failure, and neuropathic disorders in type 2 diabetes mellitus patients. Identifying reliable biomarkers promptly is pivotal for early detection and intervention in these severe complications. AREAS COVERED: This review offers a thorough examination of the latest research concerning serum biomarkers for the prediction and assessment of diabetic microvascular complications. It encompasses biomarkers associated with glycation, oxidative stress, inflammation, endothelial dysfunction, basement membrane thickening, angiogenesis, and thrombosis. The review also highlights the potential of emerging biomarkers, such as microRNAs and long non-coding RNAs. EXPERT OPINION: Serum biomarkers are emerging as valuable tools for the early assessment and therapeutic guidance of diabetic microvascular complications. The biomarkers identified not only reflect the underlying pathophysiology but also align with the extent of the disease. However, further validation across diverse populations and improvement of the practicality of these biomarkers in routine clinical practice are necessary. Pursuing these objectives is essential to advance early diagnosis, risk assessment, and individualized treatment regimens for those affected by diabetes.


Subject(s)
Biomarkers , Diabetes Mellitus, Type 2 , Humans , Biomarkers/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Diabetic Angiopathies/blood , Diabetic Angiopathies/diagnosis , Diabetic Angiopathies/etiology , Diabetic Retinopathy/blood , Diabetic Retinopathy/etiology , Diabetic Retinopathy/diagnosis , Oxidative Stress , Prognosis , MicroRNAs/blood
13.
Bioorg Chem ; 151: 107717, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39153331

ABSTRACT

The approach of metabolic chemical reporters (MCRs) for labeling proteins has been widely used in the past several decades. Nevertheless, artificial side reaction generated with fully protected MCRs, termed S-glyco-modification, occurs with cysteine residues through base-promoted ß-elimination and Michael addition, leading to false positives in the proteomic identification. Therefore, next generation of MCRs, including partially protected strategy and modifications on the backbone of monosaccharides, have emerged to improve the labeling efficiency. In this paper, we prepared fifteen kinds of unnatural monosaccharides to investigate the relationships of structures and S-glyco-modification labeling. Our results demonstrated that Ac4GlcNAz and Ac4GalNAz exhibited the most remarkable labeling effects among the detected compounds. Of note, Ac4ManNAz, Ac46AzGlucose and Ac46AzGalactose containing similar structures but did not show similar robust signals as them. Moreover, other modifications on the 1-, 2-, 3-, 4- and 6-site indicated minimal side reactions of S-glyco-modification, raising a possibility that subtle modifications of monosaccharide substrate may alter its role in the process of biosynthesis, for example, by change of electronegativity or enhancement of steric hindrance effects. In conclusion, our discoveries provide a new avenue to choose appropriate probe for selective label proteins in vitro and in vivo without undesired S-glyco-modification.


Subject(s)
Monosaccharides , Monosaccharides/chemistry , Molecular Structure
14.
Future Oncol ; : 1-11, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39105623

ABSTRACT

Aim: This article aims to identify risk factors for severe radiation-induced oral mucositis (RIOM) in head and neck cancer (HNC) patients. In addition, we intend to establish a predictive model in patients undergoing intensity-modulated radiotherapy. Patients & methods: In this retrospective study, several HNC patients (n = 179) treated at Zhejiang Provincial People's Hospital from January 2019 to June 2023 were considered. The recruited subjects were divided into modeling and validation groups. The experimental data on clinical characteristics and treatment were collected and analyzed to identify predictive factors for severe RIOM based on the logistic regression approach. Results: The results indicated that severe RIOM occurred in 55.3% of patients. Accordingly, significant predictors included smoking history, diabetes, concurrent chemotherapy, cumulative radiation dose and weight loss of ≥5% in relative to admission weight. A nomogram based on these factors was validated, showing excellent predictive accuracy. Conclusion: In summary, the predictive model could effectively identify high-risk patients for severe RIOM, enabling the design of targeted interventions and improving patient management during radiotherapy.


[Box: see text].

15.
Natl Sci Rev ; 11(8): nwae227, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39140006

ABSTRACT

Swarming, as a special form of mating aggregation, is most noteworthy in insects of the orders Ephemeroptera, Diptera, and Trichoptera. Swarming in extant trichopterans is well understood in terms of sex composition, specific mating behaviors, and functional morphological specializations of adults, but an exploration of the evolution of such aggregative behaviors is hampered by the dearth of available examples from the fossil record as well as the ability to reliably distinguish the few gatherings as the result of swarming relative to other taphonomic or behavioral factors. Herein we describe five new fossil species of caddisflies preserved in mid-Cretaceous amber from Myanmar, all preserved as large aggregations. Monospecific aggregations of these five new species can be positively identified as swarms based on morphological traits of wing shape, as well as the presence of particular forms of sexual dimorphism. Results of a phylogenetic reconstruction of both molecular and morphological data as well as ancestral-trait reconstructions and tip-dating analyses indicate that swarming was likely present in the Triassic as a feature of the trichopteran groundplan. Since most Mesozoic insectivorous predators were diurnal based on morphological evidence, largely nocturnal caddisflies would have been freed from such pressures. The phylogeny also shows a correlation between the rise of nocturnal bat predators from the Paleocene or early Eocene and the repeated loss of swarming from various clades of caddisflies, revealing the potential impact of bat predation on reshaping the behavioral landscape of Trichoptera during the Cenozoic.

16.
Autophagy ; : 1-20, 2024 Aug 04.
Article in English | MEDLINE | ID: mdl-39099169

ABSTRACT

Disruption of mitochondrial function is observed in multiple drug-induced liver injuries (DILIs), a significant global health threat. However, how the mitochondrial dysfunction occurs and whether maintain mitochondrial homeostasis is beneficial for DILIs remains unclear. Here, we show that defective mitophagy by OPTN (optineurin) ablation causes disrupted mitochondrial homeostasis and aggravates hepatocytes necrosis in DILIs, while OPTN overexpression protects against DILI depending on its mitophagic function. Notably, mass spectrometry analysis identifies a new mitochondrial substrate, GCDH (glutaryl-CoA dehydrogenase), which can be selectively recruited by OPTN for mitophagic degradation, and a new cofactor, VCP (valosin containing protein) that interacts with OPTN to stabilize BECN1 during phagophore assembly, thus boosting OPTN-mediated mitophagy initiation to clear damaged mitochondria and preserve mitochondrial homeostasis in DILIs. Then, the accumulation of OPTN in different DILIs is further validated with a protective effect, and pyridoxine is screened and established to alleviate DILIs by inducing OPTN-mediated mitophagy. Collectively, our findings uncover a dual role of OPTN in mitophagy initiation and implicate the preservation of mitochondrial homeostasis via inducing OPTN-mediated mitophagy as a potential therapeutic approach for DILIs.Abbreviation: AILI: acetaminophen-induced liver injury; ALS: amyotrophic lateral sclerosis; APAP: acetaminophen; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CHX: cycloheximide; Co-IP: co-immunoprecipitation; DILI: drug-induced liver injury; FL: full length; GCDH: glutaryl-CoA dehydrogenase; GOT1/AST: glutamic-oxaloacetic transaminase 1; GO: gene ontology; GSEA: gene set enrichment analysis; GPT/ALT: glutamic - pyruvic transaminase; INH: isoniazid; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MMP: mitochondrial membrane potential; MST: microscale thermophoresis; MT-CO2/COX-II: mitochondrially encoded cytochrome c oxidase II; OPTN: optineurin; PINK1: PTEN induced kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; TIMM23: translocase of inner mitochondrial membrane 23; TOMM20: translocase of outer mitochondrial membrane 20; TSN: toosendanin; VCP: valosin containing protein, WIPI2: WD repeat domain, phosphoinositide interacting 2.

17.
Mol Neurobiol ; 2024 Aug 24.
Article in English | MEDLINE | ID: mdl-39180695

ABSTRACT

Alcohol Use Disorder (AUD), characterized by repeated alcohol consumption and withdrawal symptoms, poses a significant public health issue. Alcohol-induced impairment of the intestinal barrier results in alterations in intestinal permeability and the composition of the intestinal microbiota. Such alterations lead to a reduced relative abundance of intestinal lactic acid bacteria. However, the role of gut microbiota in alcohol consumption is not yet fully understood. In this study, we explore the mechanism by which gut microbiota regulates alcohol consumption, specifically using extracellular vesicles derived from Lactobacillus plantarum (L-EVs). L-EVs were administered to Sprague-Dawley rats either through intraperitoneal injection or microinjection into the ventral tegmental area (VTA), resulting in a significant reduction in alcohol consumption 72 hours after withdrawal. The observed reduction was akin to the effect of an intra-VTA microinjection of Brain-Derived Neurotrophic Factor (BDNF). Intriguingly, the microinjection of K252a (a Trk B antagonist) into the VTA blocked the reducing effect of L-EVs on alcohol consumption. The intraperitoneal injection of L-EVs restored the diminished BDNF expression in the VTA of alcohol-dependent rats. Furthermore, L-EVs rescued the low BDNF expression in alcohol-incubated PC12 cells. In conclusion, our study demonstrates that L-EVs attenuated alcohol consumption by enhancing BDNF expression in alcohol-dependent rats, thus suggesting the significant therapeutic potential of L-EVs in preventing excessive alcohol consumption.

18.
Front Biosci (Landmark Ed) ; 29(8): 300, 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39206907

ABSTRACT

BACKGROUND: As a common drug for tumor therapy, doxorubicin hydrochloride (DOX) is not yet widely used as a clinical solution. This is due to its toxicity and potential drug resistance. OBJECTIVE: This study investigated the inhibitory effect of enteromorpha prolifera polysaccaharide (EPP) combined with doxorubicin hydrochloride (DOX) on A549 cells, which fall into the cell line of human non-small cell lung cancer (NSCLC). It also explained the attenuated and synergistic effect of enteromorpha acid polysaccharide along with its synergistic effect on DOX. METHODS: To evaluate the proliferation inhibitory effect of EPP, DOX and both combined, we monitored cell growth curve and morphology using the real-time cell function analysis and imaging system-xCELLigence RTCA eSight system (eSight system). Flow cytometry was used to monitor cell apoptosis rate and cell cycle distribution. Mitochondrial function was tested by the energy metabolism analysis system. RESULTS: EPP could work with DOX to inhibit the proliferation of A549 cells. Growth curve showed that when 0.4 mg/mL of EPP was mixed with 0.2 µg/mL of DOX for 24 h, the mixure liquid had a significant inhibitory effect on the proliferation of A549 cells (p < 0.0001). The cells had lower cell adhesiveness, shrinking cell membrane, cytoplasmic aggregation, and hyperchromatic nuclei. According to the flow cytometry results, the combined drug of EPP and DOX could significantly increase the apoptosis rate of A549 cells (p < 0.0001), and block the cell cycle in the G1-S phase. Based on the results of the real-time energy metabolism, we found that the combined drug could significantly reduce A549 cells' ATP production rate and inhibit their mitochondrial respiratory function. CONCLUSIONS: The combination of EPP and DOX can block cell cycle, inhibit cell mitochondrial function, promote cell apoptosis, and enhance the killing ability of DOX on tumor cells. This study supports the antitumor activity of enterococcus acid polysaccharide and provides insights on reducing doxorubicin toxicity and drug resistance. It holds great significance for applying traditional Chinese natural medicine in clinical disease treatment.


Subject(s)
Apoptosis , Cell Proliferation , Doxorubicin , Drug Synergism , Humans , Doxorubicin/pharmacology , A549 Cells , Apoptosis/drug effects , Cell Proliferation/drug effects , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Cell Cycle/drug effects , Mitochondria/drug effects , Mitochondria/metabolism , Oligosaccharides/pharmacology , Edible Seaweeds , Ulva
19.
Int Immunopharmacol ; 139: 112589, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39032468

ABSTRACT

Circadian rhythms play a crucial role in regulating various physiological processes, including specific immune functions that enhance the body's ability to anticipate and respond to threats effectively. However, research on the impact of circadian rhythms on osteoimmunology remains limited. Our study uncovered that circadian disruption leads to bone mass loss by reducing the population of Treg cells in the bone marrow. Furthermore, we observed a significant decrease in serum IL-10 cytokine levels in jet lagged mice. In our current investigation, we explored the anti-osteoclastogenic effects of IL-10 and found that IL-10 inhibits RANKL-induced osteoclastogenesis in a dose-dependent manner. Our findings suggest that the diminished anti-osteoclastogenic properties of Tregs under circadian disruption are mediated by IL-10 cytokine production. Moreover, our discoveries propose that administration of IL-10 or butyrate could potentially reverse bone mass loss in individuals experiencing jet lag.


Subject(s)
Circadian Clocks , Interleukin-10 , Mice, Inbred C57BL , T-Lymphocytes, Regulatory , Animals , Interleukin-10/metabolism , T-Lymphocytes, Regulatory/immunology , Circadian Clocks/immunology , Mice , Male , RANK Ligand/metabolism , Osteogenesis/drug effects , Jet Lag Syndrome/immunology , Osteoclasts/immunology , Osteoclasts/metabolism , Osteoclasts/drug effects , Bone Resorption/immunology , Circadian Rhythm/immunology , Cells, Cultured
20.
Front Chem ; 12: 1427670, 2024.
Article in English | MEDLINE | ID: mdl-39010937

ABSTRACT

Introduction: Tripterygium species have been traditionally used in Chinese medicine for treating various conditions. The aim of the study was to construct a drug-modified renal infarction targeting liposome (rTor-LIP) containing Tripterygium in order to improve the therapeutic effect on renal injury. Methods: rTor-LIP was prepared using the extruder method containing Tripterygium solution. The preparation was characterized by transmission electron microscopy, Marvin laser particle size analyzer, and Western blotting. In vitro experiments were conducted to verify the biocompatibility of rTor-LIP, and in vivo experiments were conducted to verify the therapeutic effect of rTor- LIP on renal injury. Results and discussion: The surface of rTor-LIP was regular and oval. In vitro results showed that after co-incubation with rTor-LIP, endothelial cells did not show significant apoptosis, and there were no significant abnormalities in the mitochondrial metabolism. The in vivo results showed that the morphology of endothelial cells in the rTor-LIP group was uniform and the cytoplasmic striations were clear, but the local striations had disappeared. Thus, rTor-LIP nano-targeted liposomes can effectively target hypoxic kidney tissue, providing a new idea for the treatment of renal infarction.

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