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1.
Front Microbiol ; 15: 1362880, 2024.
Article En | MEDLINE | ID: mdl-38699476

Cyanobacteria, which have a photoautotrophic lifestyle, are threatened by ultraviolet solar rays and the reactive oxygen species generated during photosynthesis. They can adapt to environmental conditions primarily because of their DNA damage response and repair mechanisms, notably an efficient homologous recombination repair system. However, research on double-strand break (DSB) repair pathways, including the Holliday junction (HJ) resolution process, in Synechocystis sp. PCC6803 is limited. Here, we report that SynRuvC from cyanobacteria Synechocystis sp. PCC6803 has classical HJ resolution activity. We investigated the structural specificity, sequence preference, and biochemical properties of SynRuvC. SynRuvC strongly preferred Mn2+ as a cofactor, and its cleavage site predominantly resides within the 5'-TG↓(G/A)-3' sequence. Interestingly, novel flap endonuclease and replication fork intermediate cleavage activities of SynRuvC were also determined, which distinguish it from other reported RuvCs. To explore the effect of SynRuvC on cell viability, we constructed a knockdown mutant and an overexpression strain of Synechocystis sp. PCC6803 (synruvCKD and synruvCOE) and assessed their survival under a variety of conditions. Knockdown of synruvC increased the sensitivity of cells to MMS, HU, and H2O2. The findings suggest that a novel RuvC family HJ resolvase SynRuvC is important in a variety of DNA repair processes and stress resistance in Synechocystis sp. PCC6803.

2.
BMC Cancer ; 24(1): 438, 2024 Apr 09.
Article En | MEDLINE | ID: mdl-38594670

PURPOSE: Based on the quantitative and qualitative features of CT imaging, a model for predicting the invasiveness of ground-glass nodules (GGNs) was constructed, which could provide a reference value for preoperative planning of GGN patients. MATERIALS AND METHODS: Altogether, 702 patients with GGNs (including 748 GGNs) were included in this study. The GGNs operated between September 2020 and July 2022 were classified into the training group (n = 555), and those operated between August 2022 and November 2022 were classified into the validation group (n = 193). Clinical data and the quantitative and qualitative features of CT imaging were harvested from these patients. In the training group, the quantitative and qualitative characteristics in CT imaging of GGNs were analyzed by using performing univariate and multivariate logistic regression analyses, followed by constructing a nomogram prediction model. The differentiation, calibration, and clinical practicability in both the training and validation groups were assessed by the nomogram models. RESULTS: In the training group, multivariate logistic regression analysis disclosed that the maximum diameter (OR = 4.707, 95%CI: 2.06-10.758), consolidation/tumor ratio (CTR) (OR = 1.027, 95%CI: 1.011-1.043), maximum CT value (OR = 1.025, 95%CI: 1.004-1.047), mean CT value (OR = 1.035, 95%CI: 1.008-1.063; P = 0.012), spiculation sign (OR = 2.055, 95%CI: 1.148-3.679), and vascular convergence sign (OR = 2.508, 95%CI: 1.345-4.676) were independent risk parameters for invasive adenocarcinoma. Based on these findings, we established a nomogram model for predicting the invasiveness of GGN, and the AUC was 0.910 (95%CI: 0.885-0.934) and 0.902 (95%CI: 0.859-0.944) in the training group and the validation group, respectively. The internal validation of the Bootstrap method showed an AUC value of 0.905, indicating a good differentiation of the model. Hosmer-Lemeshow goodness of fit test for the training and validation groups indicated that the model had a good fitting effect (P > 0.05). Furthermore, the calibration curve and decision analysis curve of the training and validation groups reflected that the model had a good calibration degree and clinical practicability. CONCLUSION: Combined with the quantitative and qualitative features of CT imaging, a nomogram prediction model can be created to forecast the invasiveness of GGNs. This model has good prediction efficacy for the invasiveness of GGNs and can provide help for the clinical management and decision-making of GGNs.


Adenocarcinoma of Lung , Lung Neoplasms , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/surgery , Lung Neoplasms/pathology , Nomograms , Tomography, X-Ray Computed/methods , Neoplasm Invasiveness/pathology , Adenocarcinoma of Lung/diagnostic imaging , Adenocarcinoma of Lung/surgery , Adenocarcinoma of Lung/pathology , Retrospective Studies
3.
Ageing Res Rev ; 96: 102286, 2024 Apr.
Article En | MEDLINE | ID: mdl-38561044

Chemokines and their corresponding receptors play crucial roles in orchestrating inflammatory and immune responses, particularly in the context of pathological conditions disrupting the internal environment. Among these receptors, CCR5 has garnered considerable attention due to its significant involvement in the inflammatory cascade, serving as a pivotal mediator of neuroinflammation and other inflammatory pathways associated with various diseases. However, a notable gap persists in comprehending the intricate mechanisms governing the interplay between CCR5 and its ligands across diverse and intricate inflammatory pathologies. Further exploration is warranted, especially concerning the inflammatory cascade instigated by immune cell infiltration and the precise binding sites within signaling pathways. This study aims to illuminate the regulatory axes modulating signaling pathways in inflammatory cells by providing a comprehensive overview of the pathogenic processes associated with CCR5 and its ligands across various disorders. The primary focus lies on investigating the pathomechanisms associated with CCR5 in disorders related to neuroinflammation, alongside the potential impact of aging on these processes and therapeutic interventions. The discourse culminates in addressing current challenges and envisaging potential future applications, advocating for innovative research endeavors to advance our comprehension of this realm.


Neuroinflammatory Diseases , Receptors, CCR5 , Humans , Receptors, CCR5/metabolism , Signal Transduction
4.
Microbiol Spectr ; 12(5): e0375623, 2024 May 02.
Article En | MEDLINE | ID: mdl-38534119

Zur (zinc uptake regulator) is a significant member of the Fur (ferric uptake regulator) superfamily, which is widely distributed in bacteria. Zur plays crucial roles in zinc homeostasis and influences cell development and environmental adaptation in various species. Yersinia pseudotuberculosis is a Gram-negative enteric that pathogen usually serves as a model organism in pathogenicity studies. The regulatory effects of Zur on the zinc transporter ZnuABC and the protein secretion system T6SS have been documented in Y. pseudotuberculosis. In this study, a comparative transcriptomics analysis between a ∆zur mutant and the wild-type (WT) strain of Y. pseudotuberculosis was conducted using RNA-seq. This analysis revealed global regulation by Zur across multiple functional categories, including membrane transport, cell motility, and molecular and energy metabolism. Additionally, Zur mediates the homeostasis not only of zinc but also ferric and magnesium in vivo. There was a notable decrease in 35 flagellar biosynthesis and assembly-related genes, leading to reduced swimming motility in the ∆zur mutant strain. Furthermore, Zur upregulated multiple simple sugar and oligopeptide transport system genes by directly binding to their promoters. The absence of Zur inhibited biofilm formation as well as reduced resistance to chloramphenicol and acidic stress. This study illustrates the comprehensive regulatory functions of Zur, emphasizing its importance in stress resistance and pathogenicity in Y. pseudotuberculosis. IMPORTANCE: Bacteria encounter diverse stresses in the environment and possess essential regulators to modulate the expression of genes in responding to the stresses for better fitness and survival. Zur (zinc uptake regulator) plays a vital role in zinc homeostasis. Studies of Zur from multiple species reviewed that it influences cell development, stress resistance, and virulence of bacteria. Y. pseudotuberculosis is an enteric pathogen that serves a model organism in the study of pathogenicity, virulence factors, and mechanism of environmental adaptation. In this study, transcriptomics analysis of Zur's regulons was conducted in Y. pseudotuberculosis. The functions of Zur as a global regulator in metal homeostasis, motility, nutrient acquisition, glycan metabolism, and nucleotide metabolism, in turn, increasing the biofilm formation, stress resistance, and virulence were reviewed. The importance of Zur in environmental adaptation and pathogenicity of Y. pseudotuberculosis was emphasized.


Bacterial Proteins , Biofilms , Gene Expression Regulation, Bacterial , Homeostasis , Yersinia pseudotuberculosis , Zinc , Yersinia pseudotuberculosis/genetics , Yersinia pseudotuberculosis/metabolism , Yersinia pseudotuberculosis/physiology , Biofilms/growth & development , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Zinc/metabolism , Stress, Physiological , Metals/metabolism , Virulence/genetics , Repressor Proteins/genetics , Repressor Proteins/metabolism
5.
Sci Adv ; 10(8): eadk8297, 2024 Feb 23.
Article En | MEDLINE | ID: mdl-38394201

HIV-1 Gag proteins can multimerize upon the viral genomic RNA or multiple random cellular messenger RNAs to form a virus particle or a virus-like particle, respectively. To date, whether the two types of particles form via the same Gag multimerization process has remained unclarified. Using photoactivated localization microscopy to illuminate Gag organizations and dynamics at the nanoscale, here, we showed that genomic RNA mediates Gag multimerization in a more cluster-centric, cooperative, and spatiotemporally coordinated fashion, with the ability to drive dense Gag clustering dependent on its ability to act as a long-stranded scaffold not easily attainable by cellular messenger RNAs. These differences in Gag multimerization were further shown to affect downstream selective protein sorting into HIV membranes, indicating that the choice of RNA for packaging can modulate viral membrane compositions. These findings should advance the understanding of HIV assembly and further benefit the development of virus-like particle-based therapeutics.


HIV Infections , RNA, Viral , Humans , RNA, Viral/genetics , RNA, Viral/metabolism , Cell Membrane/metabolism , Gene Products, gag/genetics , Gene Products, gag/metabolism , RNA, Messenger/metabolism , HIV Infections/metabolism , Protein Multimerization
6.
Emerg Microbes Infect ; 13(1): 2321994, 2024 Dec.
Article En | MEDLINE | ID: mdl-38377136

Vaccines utilizing modified messenger RNA (mRNA) technology have shown robust protective efficacy against SARS-CoV-2 in humans. As the virus continues to evolve in both human and non-human hosts, risk remains that the performance of the vaccines can be compromised by new variants with strong immune escape abilities. Here we present preclinical characterizations of a novel bivalent mRNA vaccine RQ3025 for its safety and effectiveness in animal models. The mRNA sequence of the vaccine is designed to incorporate common mutations on the SARS-CoV-2 spike protein that have been discovered along the evolutionary paths of different variants. Broad-spectrum, high-titer neutralizing antibodies against multiple variants were induced in mice (BALB/c and K18-hACE2), hamsters and rats upon injections of RQ3025, demonstrating advantages over the monovalent mRNA vaccines. Effectiveness in protection against several newly emerged variants is also evident in RQ3025-vaccinated rats. Analysis of splenocytes derived cytokines in BALB/c mice suggested that a Th1-biased cellular immune response was induced by RQ3025. Histological analysis of multiple organs in rats following injection of a high dose of RQ3025 showed no evidence of pathological changes. This study proves the safety and effectiveness of RQ3025 as a broad-spectrum vaccine against SARS-CoV-2 variants in animal models and lays the foundation for its potential clinical application in the future.


COVID-19 , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Cricetinae , Humans , Mice , Rats , Animals , Vaccines, Combined , SARS-CoV-2/genetics , mRNA Vaccines , COVID-19 Vaccines/genetics , COVID-19/prevention & control , Broadly Neutralizing Antibodies , Mice, Inbred BALB C , RNA, Messenger/genetics
7.
Zhongguo Zhong Yao Za Zhi ; 49(1): 55-61, 2024 Jan.
Article Zh | MEDLINE | ID: mdl-38403338

The theory of kidney storing essence storage, an important part of the basic theory of traditional Chinese medicine(TCM), comes from the Chapter 9 Discussion on Six-Plus-Six System and the Manifestations of the Viscera in the Plain Questions, which says that "the kidney manages closure and is the root of storage and the house of Jing(Essence)". According to this theory, essence is the fundamental substance of human life activities and it is closely related to the growth and development of the human body. Alzheimer's disease(AD) is one of the common neurodegenerative diseases, with the main pathological features of Aß deposition and Tau phosphorylation, which activate neurotoxic reactions and eventually lead to neuronal dysfunction and cell death, severely impairing the patient's cognitive and memory functions. Although research results have been achieved in the TCM treatment of AD, the complex pathogenesis of AD makes it difficult to develop the drugs capable of curing AD. The stem cell therapy is an important method to promote self-repair and regeneration, and bone marrow mesenchymal stem cells(BMSCs) as adult stem cells have the ability of multi-directional differentiation. By reviewing the relevant literature, this paper discusses the association between BMSCs and the TCM theory of kidney storing essence, and expounds the material basis of this theory from the perspective of molecular biology. Studies have shown that TCM with the effect of tonifying the kidney in the treatment of AD are associated with BMSCs. Exosomes produced by such cells are one of the main substances affecting AD. Exosomes containing nucleic acids, proteins, and lipids can participate in intercellular communication, regulate cell function, and affect AD by reducing Aß deposition, inhibiting Tau protein phosphorylation and neuroinflammation, and promoting neuronal regeneration. Therefore, discussing the prevention and treatment of exosomes and AD based on the theory of kidney storing essence will provide a new research idea for the TCM treatment of AD.


Alzheimer Disease , Exosomes , Adult , Humans , Alzheimer Disease/prevention & control , Alzheimer Disease/drug therapy , Exosomes/metabolism , Exosomes/pathology , Kidney/pathology , Medicine, Chinese Traditional , Neurons
8.
Mini Rev Med Chem ; 2024 Jan 11.
Article En | MEDLINE | ID: mdl-38213172

Ginsenoside is the principal active ingredient in ginseng. Several investigations have found that ginsenosides have anti-inflammatory, antioxidant, anti-apoptotic, anti-cancer, and antiallergic activities. Ferroptosis is an iron-dependent, non-apoptotic form of cell-regulated death caused by lipid peroxidation. Iron, lipid, and amino acid metabolism orchestrate the complex ferroptosis response through direct or indirect regulation of iron accumulation or lipid peroxidation. More and more research has demonstrated that ginsenoside impacts illnesses via ferroptosis, implying that ferroptosis might be employed as a novel target of ginsenoside for disease therapy. This article examines the molecular mechanism of ferroptosis as well as the current advancement of ginsenoside in influencing disorders via ferroptosis.

9.
Phytomedicine ; 123: 155238, 2024 Jan.
Article En | MEDLINE | ID: mdl-38128394

BACKGROUND: Ischemic stroke, a severe and life-threatening neurodegenerative condition, currently relies on thrombolytic therapy with limited therapeutic window and potential risks of hemorrhagic transformation. Thus, there is a crucial need to explore novel therapeutic agents for ischemic stroke. Ginsenoside Rg1 (Rg1), a potential neuroprotective agent, exhibits anti-ischemic effects attributed to its anti-inflammatory, anti-oxidant, and anti-apoptotic properties. Nevertheless, the precise underlying mechanism of action remains to be fully elucidated. PURPOSE: This study aimed to explore whether Rg1 exerts anti-ischemic stroke effects by inhibiting pyroptotic neuronal cell death through modulation of the chemokine like factor 1 (CKLF1)/ C-C chemokine receptor type 5 (CCR5) axis. METHODS: In this study, the MCAO model was used as an ischemic stroke model, and experimental tests were performed after 6 hours of ischemia. The anti-ischemic effect of Rg1 was examined by TTC staining, nissl-staining and neurobehavioral tests. In the in vitro experiments, PC12 cells were subjected to stimulation with CKLF1's mimetic peptide C27 to assess the potential of CKLF1 to induce focal neuronal cell death. Additionally, the impact of CKLF1 mimetic peptide C27, antagonistic peptide C19, and CCR5 inhibitor MVC on PC12 cells subjected to oxygen-glucose deprivation (OGD) and subsequently treated with Rg1 was investigated. In vivo, Rg1 treatment was examined by quantitative real-time PCR (qPCR), ELISA, immunohistochemistry (IHC), immunofluorescence (IF), western blot (WB), and co-immunoprecipitate (Co-IP) assays to perspective whether Rg1 treatment reduces CKLF1/CCR5 axis-induced pyroptotic neuronal cell death. In addition, to further explore the biological significance of CKLF1 in ischemic stroke, CKLF1-/- rats were used as the observation subjects in this study. RESULTS: The in vitro results suggested that CKLF1 was able to induce neuronal cells to undergo pyroptosis. In vivo pharmacodynamic results showed that Rg1 treatment was able to significantly improve symptoms in ischemic stroke rats. In addition, Rg1 treatment was able to inhibit the interaction between CKLF1 and CCR5 after ischemic stroke and inhibited CKLF1/CCR5 axis-induced pyroptosis. The results of related experiments in CKLF1-/- rats showed that Rg1 lost its therapeutic effect after CKLF1 knockdown. CONCLUSION: Our findings indicate that the activation of the NLRP3 inflammasome is initiated by the CKLF1/CCR5 axis, facilitated through the activation of the NF-κB pathway, ultimately resulting in the pyroptosis of neuronal cells. Conversely, Rg1 demonstrates the capability to mitigate neuronal cell damage following CKLF1-induced effects by suppressing the expression of CKLF1. Thus, CKLF1 represents a crucial target for Rg1 in the context of cerebral ischemia treatment, and it also holds promise as a potential target for drug screening in the management of ischemic stroke.


Brain Ischemia , Ginsenosides , Ischemic Stroke , Reperfusion Injury , Humans , Rats , Animals , Ischemic Stroke/drug therapy , Pyroptosis , Receptors, Chemokine/therapeutic use , Brain Ischemia/drug therapy , Brain Ischemia/metabolism , Reperfusion Injury/drug therapy , Receptors, CCR5/therapeutic use
10.
Eur J Pharmacol ; 963: 176264, 2024 Jan 15.
Article En | MEDLINE | ID: mdl-38123006

AIMS: Ischemic stroke is a severe cerebrovascular disease in which neuronal death continually occurs through multiple forms, including apoptosis, autophagy, pyroptosis and ferroptosis. Quercetin (QRC), as a natural flavonoid compound, has been reported to have pharmacological effects on ischemic injury accompanied by unclear anti-ferroptotic mechanisms. This study is designed to investigate the therapeutic effects of QRC against ferroptosis in ischemic stroke. MATERIALS AND METHODS: In vivo, the model of MCAO rats were used to assess the protective effect of QRC on cerebral ischemic. Additionally, we constructed oxidative stressed and ferroptotic cell models to explore the effects and mechanisms of QRC on ferroptosis. The related proteins were analysed by western blotting, immunohistochemical and immunofluorescence techniques. RESULTS: The experiments demonstrated that QRC improves neurological deficits, infarct volume, and pathological features in MCAO rats, also increased the viability of HT-22 cells exposed to H2O2 and erastin. These results, including MDA, SOD, GSH, ROS levels and iron accumulation, indicated that QRC suppresses the generation of lipid peroxides and may involve in the regulatory of ferroptosis. Both in vitro and in vivo, QRC was found to inhibit ferroptosis by up-regulating GPX4 and FTH1, as well as down-regulating ACSL4. Furthermore, we observed that QRC enhances the nuclear translocation of Nrf2 and activates the downstream antioxidative proteins. Importantly, the effect of QRC on ferroptosis can be reversed by the Nrf2 inhibitor ML385. CONCLUSIONS: This study provides evidence that QRC has a neuroprotective effect by inhibiting ferroptosis, demonstrating the therapeutic potential for cerebral ischemic stroke.


Brain Injuries , Ferroptosis , Ischemic Stroke , Quercetin , Stroke , Animals , Rats , Ferroptosis/drug effects , Hydrogen Peroxide , NF-E2-Related Factor 2 , Quercetin/pharmacology , Quercetin/therapeutic use , Signal Transduction , Stroke/drug therapy , Heme Oxygenase (Decyclizing)/drug effects , Heme Oxygenase (Decyclizing)/metabolism
11.
J Affect Disord ; 348: 107-115, 2024 Mar 01.
Article En | MEDLINE | ID: mdl-38101523

BACKGROUND: Depression is a refractory psychiatric disorder closely associated with dysfunction of the gap junctions (GJs) between astrocytes as well as neuroinflammation. Higenamine (Hig) is a potent cardiotonic ingredient in Fuzi (i.e., Aconitum carmichaeli Debx.) with anti-inflammatory and antioxidant effects, which has a significant protective effect on damaged nerve cells and has great potential for the treatment of neuropsychiatric diseases. METHODS: Rats were stimulated by chronic unpredictable stress (CUS) for 28 days while given Hig (5, 10, 20 mg/kg) and then analyzed behaviorally by the open field test, sucrose preference test, and forced swimming test. Changes in astrocyte GJs function and morphology were observed by dye transfer and transmission electron microscopy, respectively. Expression and phosphorylation of connexin 43 (Cx43) were analyzed by Western blot. Also, considering the close relationship between depression and neuroinflammation, we determined the inflammatory response in serum with ELISA kits and analyzed the expression of inflammation-related proteins with Western blot. RESULTS: Hig ameliorated CUS-induced depression-like behavior in rats. Hig administration improved gap junctional dysfunction in astrocytes, reduced gap junctional gaps and elevated the expression of Cx43 and decreased the phosphorylation of Cx43. Meanwhile, Hig administration was also able to attenuate the inflammatory response that occurs after CUS in rats. LIMITATIONS: For the role of Cx43 in depression, we did not validate it more deeply in animal models with knockout Cx43. In addition, GJs dysfunction might be associated with the inflammatory response seen in depression, but this needs to be further investigated. CONCLUSIONS: Hig ameliorates depression and exerts its antidepressant effect possibly by improving the dysfunctional GJs between astrocytes and the inflammatory response.


Alkaloids , Astrocytes , Connexin 43 , Tetrahydroisoquinolines , Humans , Rats , Animals , Connexin 43/metabolism , Connexin 43/pharmacology , Neuroinflammatory Diseases , Gap Junctions/metabolism , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Antidepressive Agents/metabolism
12.
Materials (Basel) ; 16(24)2023 Dec 12.
Article En | MEDLINE | ID: mdl-38138756

Currently, the development of nonmetallic oxygen reduction reaction (ORR) catalysts based on heteroatomic-doped carbon materials is receiving increaseing attention in the field of fuel cells. Here, we used enzymolytic lignin (EL), melamine, and thiourea as carbon, nitrogen, and sulfur sources and NH4Cl as an activator to prepare N- and S-codoped lignin-based polyporous carbon (ELC) by one-step pyrolysis. The prepared lignin-derived biocarbon material (ELC-1-900) possessed a high specific surface area (844 m2 g-1), abundant mesoporous structure, and a large pore volume (0.587 cm3 g-1). The XPS results showed that ELC-1-900 was successfully doped with N and S. ELC-1-900 exhibited extremely high activity and stability in alkaline media for the ORR, with a half-wave potential (E1/2 = 0.88 V) and starting potential (Eonset = 0.98 V) superior to those of Pt/C catalysts and most non-noble-metal catalysts reported in recent studies. In addition, ELC-1-900 showed better ORR stability and methanol tolerance in alkaline media than commercial Pt/C catalysts.

13.
J Adv Res ; 2023 Nov 04.
Article En | MEDLINE | ID: mdl-37926143

BACKGROUND: Pulmonary hypertension (PH) represents a progressive condition characterized by the remodeling of pulmonary arteries, ultimately culminating in right heart failure and increased mortality rates. Substantial evidence has elucidated the pivotal role of perivascular inflammatory factors and immune dysregulation in the pathogenesis of PH. Chemokines, a class of small secreted proteins, exert precise control over immune cell recruitment and functionality, particularly with respect to their migration to sites of inflammation. Consequently, chemokines emerge as critical drivers facilitating immune cell infiltration into the pulmonary tissue during inflammatory responses. This review comprehensively examines the significant contributions of CC chemokines in the maintenance of immune cell homeostasis and their pivotal role in regulating inflammatory responses. The central focus of this discussion is directed towards elucidating the precise immunoregulatory actions of CC chemokines concerning various immune cell types, including neutrophils, monocytes, macrophages, lymphocytes, dendritic cells, mast cells, eosinophils, and basophils, particularly in the context of pH processes. Furthermore, this paper delves into an exploration of the underlying pathogenic mechanisms that underpin the development of PH. Specifically, it investigates processes such as cellular pyroptosis, examines the intricate crosstalk between bone morphogenetic protein receptor type 2 (BMPR2) mutations and the immune response, and sheds light on key signaling pathways involved in the inflammatory response. These aspects are deemed critical in enhancing our understanding of the complex pathophysiology of PH. Moreover, this review provides a comprehensive synthesis of findings from experimental investigations targeting immune cells and CC chemokines. AIM OF REVIEW: In summary, the inquiry into the inflammatory responses mediated by CC chemokines and their corresponding receptors, and their potential in modulating immune reactions, holds promise as a prospective avenue for addressing PH. The potential inhibition of CC chemokines and their receptors stands as a viable strategy to attenuate the inflammatory cascade and ameliorate the pathological manifestations of PH. Nonetheless, it is essential to acknowledge the current state of clinical trials and the ensuing progress, which regrettably appears to be less than encouraging. Substantial hurdles exist in the successful translation of research findings into clinical applications. The intention is that such emphasis could potentially foster the advancement of potent therapeutic agents presently in the process of clinical evaluation. This, in turn, may further bolster the potential for effective management of PH.

14.
Biomed Pharmacother ; 167: 115545, 2023 Nov.
Article En | MEDLINE | ID: mdl-37734259

Hypericin is widely utilized for its precise antidepressant properties, but its exact antidepressant mechanism remains unclear. Gap junctions, which were predominantly expressed in astrocytes in the central nervous system, are concerned with the pathogenesis of depression. However, the role of hypericin in gap junctional dysfunction in depression has rarely been investigated. Here, we found that gap junctions were ultra-structurally broadened in the chronic unpredictable stress (CUS) rat model of depression, while hypericin repaired the dysfunction of gap junctions. Suppression of gap junctions by bilateral injection of carbenoxolone (CBX) in the prefrontal cortex of rats significantly inhibited the restoration of gap junctional dysfunction in depression by hypericin. Meanwhile, hypericin failed to show antidepressant benefits. Furthermore, in corticosterone (CORT)-stimulated primary astrocytes derived from neonatal rats, hypericin dramatically reversed the phosphorylation of connexin 43 (Cx43), normalizing the expression of Cx43 and thereby ameliorating gap junctional dysfunction. Comparatively, CBX inhibited the remission of hypericin on gap junctional intercellular communication function. Gap junctional function might be a novel therapeutic target for hypericin in the treatment of depression and provide potential novel insights into the antidepressant mechanism of other herbal ingredients.

15.
Stress Biol ; 3(1): 2, 2023 Jan 06.
Article En | MEDLINE | ID: mdl-37676351

The type VI secretion system (T6SS) is a widespread protein secretion apparatus deployed by many Gram-negative bacterial species to interact with competitor bacteria, host organisms, and the environment. Yersinia pseudotuberculosis T6SS4 was recently reported to be involved in manganese acquisition; however, the underlying regulatory mechanism still remains unclear. In this study, we discovered that T6SS4 is regulated by ferric uptake regulator (Fur) in response to manganese ions (Mn2+), and this negative regulation of Fur was proceeded by specifically recognizing the promoter region of T6SS4 in Y. pseudotuberculosis. Furthermore, T6SS4 is induced by low Mn2+ and oxidative stress conditions via Fur, acting as a Mn2+-responsive transcriptional regulator to maintain intracellular manganese homeostasis, which plays important role in the transport of Mn2+ for survival under oxidative stress. Our results provide evidence that T6SS4 can enhance the oxidative stress resistance and virulence for Y. pseudotuberculosis. This study provides new insights into the regulation of T6SS4 via the Mn2+-dependent transcriptional regulator Fur, and expands our knowledge of the regulatory mechanisms and functions of T6SS from Y. pseudotuberculosis.

16.
J Transl Med ; 21(1): 519, 2023 08 02.
Article En | MEDLINE | ID: mdl-37533007

Cardiovascular diseases (CVDs) continue to exert a significant impact on global mortality rates, encompassing conditions like pulmonary arterial hypertension (PAH), atherosclerosis (AS), and myocardial infarction (MI). Oxidative stress (OS) plays a crucial role in the pathogenesis and advancement of CVDs, highlighting its significance as a contributing factor. Maintaining an equilibrium between reactive oxygen species (ROS) and antioxidant systems not only aids in mitigating oxidative stress but also confers protective benefits on cardiac health. Herbal monomers can inhibit OS in CVDs by activating multiple signaling pathways, such as increasing the activity of endogenous antioxidant systems and decreasing the level of ROS expression. Given the actions of herbal monomers to significantly protect the normal function of the heart and reduce the damage caused by OS to the organism. Hence, it is imperative to recognize the significance of herbal monomers as prospective therapeutic interventions for mitigating oxidative damage in CVDs. This paper aims to comprehensively review the origins and mechanisms underlying OS, elucidate the intricate association between CVDs and OS, and explore the therapeutic potential of antioxidant treatment utilizing herbal monomers. Furthermore, particular emphasis will be placed on examining the cardioprotective effects of herbal monomers by evaluating their impact on cardiac signaling pathways subsequent to treatment.


Cardiovascular Diseases , Humans , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/prevention & control , Antioxidants/metabolism , Reactive Oxygen Species/metabolism , Oxidative Stress , Heart
17.
Polymers (Basel) ; 15(14)2023 Jul 21.
Article En | MEDLINE | ID: mdl-37514493

It is important to clarify the distribution of pyrolysis products from lignocellulosic biomass for its thermal transformation to produce high-quality bio-oil. Influences of the reaction temperature and catalysts on the pyrolysis product distribution from aspen wood (AW) and rice husk (RH) were studied by pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS). The difference in components from the lignocellulosic biomass results in different pyrolysis characteristics of the biomass raw materials. The reaction temperature significantly influences the product distribution from AW and RH pyrolysis. In all AW catalysis experiments, acids (8.35%), ketones (3.79%), phenols (4.73%), and esters (1.50%) have the lowest content while carbohydrates (48.75%) demonstrate the highest content when taking zinc chloride (ZnCl2) as the catalyst; the HZSM-5 molecular sieve (HZSM-5) promotes the generation of esters (7.97%) and N-compounds (22.43%) while inhibiting production of aldehydes (2.41%); addition of an MCM-41 molecular sieve (MCM-41) is conducive to increasing the contents of aldehydes (21.29%), furans (5.88%), ketones (22.30%), acids (20.46%), and hydrocarbons (4.85%), while reducing the contents of alcohols (0) and carbohydrates (0). In all RH catalysis experiments, the addition of ZnCl2 helps increase the content of carbohydrates (39.16%) and decrease the contents of ketones (3.89%), phenols (5.20%), alcohols (2.34%), esters (1.13%), and N-compounds (3.09%); when applying HZSM-5 as the catalyst, hydrocarbons (18.28%) and alcohols (6.66%) reach their highest content while acids (13.21%) have the lowest content; MCM-41 promotes the generation of aldehydes (25.33%) and furans (5.55%) while inhibiting that of carbohydrates (1.42%).

18.
J Environ Manage ; 345: 118661, 2023 Nov 01.
Article En | MEDLINE | ID: mdl-37515885

Volatile organic compounds (VOCs) evolved from biomass gasification plays a positive role in the formation of PM2.5 and odor pollution. In order to improve the removal rate of various VOCs produced by biomass gasification, a nickel-based supported HZSM-5 cataly st (Ni/HZSM-5 and Ni-Ca-Co/HZSM-5) was prepared by different auxiliary methods, Ni loadings, and pyrolysis temperatures. The catalytic cracking performance of Ni/HZSM-5 catalysts for different VOCs model compounds such as toluene, phenol, furan, acetic acid and cyclohexane were studied in a fixed-bed reactor. The catalysts were further characterized and analyzed by XRD, SEM, XPS and BET. The results showed that the Ni/HZSM--C-Co5 catalyst prepared by ultrasonic-assisted excess impregnation method with Ni loading of 8 wt%, Ca loading of 4 wt%, Co loading of 0.1 wt% had strong catalytic activity for VOCs degradation. With the increase of the cracking temperature, the conversion rate and gas yield of from model compound cracking improved significantly. At 800 °C, the conversion of each model compound was more than 90%, accompanied by the generation of cracking gases such as H2 and CH4. The selectivity of H2 and CH4 from toluene cracking reached 93%, and cyclohexane reached 98%. The models with higher oxygen content and lower bond energy were more likely to undergo reforming reaction to form small molecular gas. Model compounds with large molecular weight and high carbon content provided more carbon sources. Under the conversion degree towards the gas direction was high. This study provides a new idea on the removal of VOCs for the efficient utilization of biomass resources.


Volatile Organic Compounds , Biomass , Gases/chemistry , Catalysis , Carbon , Toluene/chemistry
19.
Asian J Surg ; 46(9): 3405-3416, 2023 Sep.
Article En | MEDLINE | ID: mdl-37328382

Several studies have revealed that computed tomography (CT) features can make a distinction in the invasive properties of pure ground-glass nodules (pGGNs). However, imaging parameters related to the invasive properties of pGGNs are unclear. This meta-analysis was designed to decipher the correlation between the invasiveness of pGGNs and CT-based features, and ultimately to be conducive to making rational clinical decisions. We searched a series of databases, including PubMed, Embase, Web of Science, Cochrane Library, Scopus, wanfang, CNKI, VIP, as well as CBM databases, until September 20, 2022, for the eligible publications only in Chinese or English. This meta-analysis was implemented with the Stata 16.0 software. Ultimately, 17 studies published between 2017 and 2022 were included. According to the meta-analysis, we observed a larger maximum size of lesions in invasive adenocarcinoma (IAC) versus that in preinvasive lesions (PIL) [SMD = 1.37, 95% CI (1.07-1.68), P < 0.05]. Meanwhile, there were also increased mean CT values of IAC [SMD = 0.71, 95% CI (0.35, 1.07), P < 0.05], the incidence of pleural traction sign [OR = 1.94, 95% CI (1.24, 3.03), P < 0.05], the incidence of IAC spiculation [OR = 1.55, 95% CI (1.05, 2.29), P < 0.05] in comparison to those of PIL. Nevertheless, IAC and PIL exhibited no significant differences in vacuole sign, air bronchogram, regular shape, lobulation and vascular convergence sign (all P > 0.05). Therefore, IAC and PIL manifested different CT features of pGGNs. The maximum diameter of lesions, mean CT value, pleural traction sign and spiculation are important indicators to distinguish IAC and PIL. Reasonable use of these features can be helpful to the treatment of pGGNs.


Adenocarcinoma , Lung Neoplasms , Humans , Lung Neoplasms/pathology , Neoplasm Invasiveness/pathology , Adenocarcinoma/pathology , Tomography, X-Ray Computed/methods , Databases, Factual , Retrospective Studies
20.
Phys Rev Lett ; 130(20): 204001, 2023 May 19.
Article En | MEDLINE | ID: mdl-37267548

In this Letter, we propose a novel strategy for significantly enhancing the heat transfer in convection turbulence. By introducing a boundary deformation of the standing-wave type, flow modulation can be realized when the amplitude is comparable or larger than the boundary-layer thickness. For a fixed moderate frequency, the entire fluid layer follows the boundary motion at small wave numbers, while only the near-wall regions are affected by the boundary deformation at large wave numbers. The heat-flux enhancement happens for the latter. For a fixed wave number and gradually increasing frequency, the vortical flows inside the wave valleys exhibit nonlinear transition and alter the distribution of boundary heat flux, and the global heat flux increases significantly at large enough frequencies. The current findings suggest that oscillating deformations of boundary can efficiently break the boundary layers, which serves as the bottleneck of global heat transfer, and open a new venue for modulating the convection turbulence.

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