Construction and validation of a nomogram to predict left ventricular hypertrophy in low-risk patients with hypertension.

Electrocardiography (ECG) is an accessible diagnostic tool for screening patients with hypertensive left ventricular hypertrophy (LVH). However, its diagnostic sensitivity is low, with a high probability of false-negatives. Thus, this study aimed to establish a clinically useful nomogram to supplement the assessment of LVH in patients with hypertension and without ECG-LVH based on Cornell product criteria (low-risk hypertensive population). A cross-sectional dataset was used for model construction and divided into development (n = 2906) and verification (n = 1447) datasets. A multivariable logistic regression risk model and nomogram were developed after screening for risk factors. Of the 4353 low-risk hypertensive patients, 673 (15.4%) had LVH diagnosed by echocardiography (Echo-LVH). Eleven risk factors were identified: hypertension awareness, duration of hypertension, age, sex, high waist-hip ratio, education level, tea consumption, hypochloremia, and other ECG-LVH diagnostic criteria (including Sokolow-Lyon, Sokolow-Lyon products, and Peguero-Lo Presti). For the development and validation datasets, the areas under the curve were 0.724 (sensitivity = 0.606) and 0.700 (sensitivity = 0.663), respectively. After including blood pressure, the areas under the curve were 0.735 (sensitivity = 0.734) and 0.716 (sensitivity = 0.718), respectively. This novel nomogram had a good predictive ability and may be used to assess the Echo-LVH risk in patients with hypertension and without ECG-LVH based on Cornell product criteria.

Carboxyl-Decorated UiO-66 Supporting Pd Nanoparticles for Efficient Room-Temperature Hydrodeoxygenation of Lignin Derivatives.

Hydrodeoxygenation (HDO) of lignin derivatives at room-temperature (RT) is still of challenge due to the lack of satisfactory activity reported in previous literature. Here, it is successfully designed a Pd/UiO-66-(COOH)2 catalyst by using UiO-66-(COOH)2 as the support with uncoordinated carboxyl groups. This catalyst, featuring a moderate Pd loading, exhibited exceptional activity in RT HDO of vanillin (VAN, a typical model lignin derivative) to 2-methoxyl-4-methylpheonol (MMP), and >99% VAN conversion with >99% MMP yield is achieved, which is the first metal-organic framework (MOF)-based catalyst realizing the goal of RT HDO of lignin derivatives, surpassing previous reports in the literature. Detailed investigations reveal a linear relationship between the amount of uncoordinated carboxyl group and MMP yield. These uncoordinated carboxyl groups accelerate the conversion of intermediate such as vanillyl alcohol (VAL), ultimately leading to a higher yield of MMP over Pd/UiO-66-(COOH)2 catalyst. Furthermore, Pd/UiO-66-(COOH)2 catalyst also exhibits exceptional reusability and excellent substrate generality, highlighting its promising potential for further biomass utilization.

Establishment and application of an iELISA detection method for measuring apical membrane antigen 1 (AMA1) antibodies of Toxoplasma gondii in cats.

BACKGROUND: Diseases caused by Toxoplasma gondii (T. gondii) have introduced serious threats to public health. There is an urgent need to develop a rapid detection method for T. gondii infection in cats, which are definitive hosts. Recombinant apical membrane antigen 1 (rAMA1) was produced in a prokaryotic expression system and used as the detection antigen. The aim of this study was to evaluate and optimize a reliable indirect enzyme-linked immunosorbent assay (iELISA) method based on rAMA1 for the detection of antibodies against T. gondii in cats. RESULTS: The rAMA1-iELISA method was developed and optimized by the chessboard titration method. There were no cross-reactions between T. gondii-positive cat serum and positive serum for other pathogens, indicating that rAMA1-iELISA could only detect T. gondii in most cases. The lowest detection limit of rAMA1-iELISA was 1:3200 (dilution of positive serum), and the CV of repeated tests within batches and between batches were confirmed to be less than 10%. The results of 247 cat serum samples detected by rAMA1-iELISA (kappa value = 0.622, p < 0.001) were in substantial agreement with commercial ELISA. The ROC curve analysis revealed the higher overall check accuracy of rAMA1-iELISA (sensitivity = 91.7%, specificity = 93.6%, AUC = 0.956, 95% CI 0.905 to 1.000) than GRA7-based iELISA (sensitivity = 91.7%, specificity = 85.5%, AUC = 0.936, 95% CI 0.892 to 0.980). Moreover, the positive rate of rAMA1-iELISA (6.5%, 16/247) was higher than that of GRA7-based iELISA (3.6%, 9/247) and that of commercial ELISA kit (4.9%, 12/247). CONCLUSION: The iELISA method with good specificity, sensitivity, and reproducibility was established and can be used for large-scale detection of T. gondii infection in clinical cat samples.

[Identification of SULF1 as a Shared Gene in Idiopathic Pulmonary Fibrosis
and Lung Adenocarcinoma].

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an idiopathic chronic, progressive interstitial lung disease with a diagnosed median survival of 3-5 years. IPF is associated with an increased risk of lung cancer. Therefore, exploring the shared pathogenic genes and molecular pathways between IPF and lung adenocarcinoma (LUAD) holds significant importance for the development of novel therapeutic approaches and personalized precision treatment strategies for IPF combined with lung cancer. METHODS: Bioinformatics analysis was conducted using publicly available gene expression datasets of IPF and LUAD from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis was employed to identify common genes involved in the progression of both diseases, followed by functional enrichment analysis. Subsequently, additional datasets were used to pinpoint the core shared genes between the two diseases. The relationship between core shared genes and prognosis, as well as their expression patterns, clinical relevance, genetic characteristics, and immune-related functions in LUAD, were analyzed using The Cancer Genome Atlas (TCGA) database and single-cell RNA sequencing datasets. Finally, potential therapeutic drugs related to the identified genes were screened through drug databases. RESULTS: A total of 529 shared genes between IPF and LUAD were identified. Among them, SULF1 emerged as a core shared gene associated with poor prognosis. It exhibited significantly elevated expression levels in LUAD tissues, concomitant with high mutation rates, genomic heterogeneity, and an immunosuppressive microenvironment. Subsequent single-cell RNA-seq analysis revealed that the high expression of SULF1 primarily originated from tumor-associated fibroblasts. This study further demonstrated an association between SULF1 expression and tumor drug sensitivity, and it identified potential small-molecule drugs targeting SULF1 highly expressed fibroblasts. CONCLUSIONS: This study identified a set of shared molecular pathways and core genes between IPF and LUAD. Notably, SULF1 may serve as a potential immune-related biomarker and therapeutic target for both diseases.

Transmission of HCoV-OC43 to pet hamsters.

Coronaviruses (CoVs) are a significant group of pathogens that pose a serious threat to both human and animal health, with some being zoonotic and displaying frequent cross-species transmission. Human CoV-OC43 (HCoV-OC43) is one of the four common human CoVs that can cause seasonal mild to moderate respiratory diseases in humans. In this study, we identified HCoV-OC43 for the first time in two asymptomatic pet hamsters, which share a high similarity with the human-derived HCoV-OC43 strain, suggesting potential cross-species transmission of HCoV-OC43 to pet hamsters. The finding emphasizes the need to strengthen pathogen monitoring of livestock and pets in close contact with humans to provide early warning of public safety.

[Progress in the Study of Spindle Assembly Checkpoint in Lung Cancer].

Spindle assembly checkpoint (SAC) is a protective mechanism for cells to undergo accurate mitosis. SAC prevented chromosome segregation when kinetochores were not, or incorrectly attached to microtubules in the anaphase of mitosis, thus avoiding aneuploid chromosomes in daughter cells. Aneuploidy and altered expression of SAC component proteins are common in different cancers, including lung cancer. Therefore, SAC is a potential new target for lung cancer therapy. Five small molecule inhibitors of monopolar spindle 1 (MPS1), an upstream component protein of SAC, have entered clinical trials. This article introduces the biological functions of SAC, summarizes the abnormal expression of SAC component proteins in various cancers and the research progress of MPS1 inhibitors, and expects to provide a reference for the future development of lung cancer therapeutic strategies targeting SAC components.
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Formosanin C inhibits non-small-cell lung cancer progression by blocking MCT4/CD147-mediated lactate export.

BACKGROUND: Tumor cells reprogram their metabolic network to maintain their uncontrolled proliferation, metastasis, and resistance to cancer therapy. Treatments targeting abnormal cellular metabolism may have promising therapeutic effects. Formosanin C (FC), a diosgenin derived from the rhizoma of Paris polyphylla var. yunnanensis, has shown potent anti-cancer activities against various cancer types. However, the effect of FC on cancer metabolism remains to be elucidated. PURPOSE: In this research, we aimed to elucidate FC's effect and potential mechanisms on metabolism in lung cancer. METHODS: Colony formation, transwell cell migration, and apoptosis were detected in multiple NSCLC cell lines to assess the cytotoxicity of FC. 1H NMR metabolomics approach was applied to screen the differential metabolites in H1299 cells and the culture medium. Western blotting, flow cytometry, and other molecular biological techniques were performed to verify the latent mechanism involved in metabolites. An allograft tumor model was employed to investigate the anti-tumor effects of FC in vivo. RESULTS: FC significantly inhibited monoclonal formation and migration and induced cell cycle arrest and apoptosis in NSCLC cells. FC altered the abundances of 12 metabolites in lung cancer cells and 3 metabolites in the medium. These differential metabolites are primarily involved in glycolysis, citric acid cycle, and glutathione pathways. Notably, there was a remarkable increase in intracellular lactate and a reduction in extracellular lactate after FC treatment. Mechanically, FC downregulated the expression of MCT4 and CD147, blocking the export of lactate. Furthermore, FC also evoked mitochondrial dysfunction coupled with excessive oxidative stress, decreased mitochondrial membrane potential, ATP production reduction, glutathione depletion, and Ca2+ overload. Moreover, FC suppressed tumor progression in vivo with reduced protein levels of the MCT4 and CD147 in tumor tissues. CONCLUSION: FC inhibits lung cancer growth by the novel mechanism in which MCT4/CD147-mediated inhibition of lactate transport and disruption of mitochondrial functions are involved.

Novel Anticancer Strategy by Targeting the Gut Microbial Neurotransmitter Signaling to Overcome Immunotherapy Resistance.

Significance: Microbial neurotransmitters, as potential targets for cancer therapy, are expected to provide a new perspective on the interaction between the gut microbiome and cancer immunotherapy. Recent Advances: Mounting data reveal that most neurotransmitters can be derived from gut microbiota. Furthermore, modulation of neurotransmitter signaling can limit tumor growth and enhance antitumor immunity. Critical Issues: Here, we first present the relationships between microbial neurotransmitters and cancer cells mediated by immune cells. Then, we discuss the microbial neurotransmitters recently associated with cancer immunotherapy. Notably, the review emphasizes that neurotransmitter signaling plays a substantial role in cancer immunotherapy as an emerging cancer treatment target by regulating targeted receptors and interfering with the tumor microenvironment. Future Directions: Future studies are required to uncover the antitumor mechanisms of neurotransmitter signaling to develop novel treatment strategies to overcome cancer immunotherapy resistance. Antioxid. Redox Signal. 38, 298-315.

Suppression of PD-L1 release from small extracellular vesicles promotes systemic anti-tumor immunity by targeting ORAI1 calcium channels.

Blockade of immune checkpoints as a strategy of cancer cells to overcome the immune response has received ample attention in cancer research recently. In particular, expression of PD-L1 by various cancer cells has become a paradigm in this respect. Delivery of PD-L1 to its site of action occurs either by local diffusion, or else by transport via small extracellular vesicles (sEVs, commonly referred to as exosomes). Many steps of sEVs formation, their packaging with PD-L1 and their release into the extracellular space have been studied in detail. The likely dependence of release on Ca2+ -signaling, however, has received little attention. This is surprising, since the intracellular Ca2+ -concentration is known as a prominent regulator of many secretory processes. Here, we report on the roles of three Ca2+ -dependent proteins in regulating release of PD-L1-containing sEVs, as well as on the growth of tumors in mouse models. We show that sEVs release in cancer cell lines is Ca2+ -dependent and the knockdown of the gene coding the Ca2+ -channel protein ORAI1 reduces Ca2+ -signals and release of sEVs. Consequently, the T cell response is reinvigorated and tumor progression in mouse models is retarded. Furthermore, analysis of protein expression patterns in samples from human cancer tissue shows that the ORAI1 gene is significantly upregulated. Such upregulation is identified as an unfavorable prognostic factor for survival of patients with non-small-cell lung cancer. We show that reduced Ca2+ -signaling after knockdown of ORAI1 gene also compromises the activity of melanophilin and Synaptotagmin-like protein 2, two proteins, which are important for correct localization of secretory organelles within cancer cells and their transport to sites of exocytosis. Thus, the Ca2+ -channel ORAI1 and Ca2+ -dependent proteins of the secretion pathway emerge as important targets for understanding and manipulating immune checkpoint blockade by PD-L1.

Novel study on the prevalence of Trichinella spiralis in farmed American minks (Neovison vison) associated with exposure to wild rats (Rattus norvegicus) in China.

Minks and brown rats are reservoir hosts for many endoparasites including those of the genus Trichinella, a group of parasite nematodes with a worldwide distribution. However, little is known about the prevalence of Trichinella sp. infection in the American mink (Neovison vison) and rats (Rattus norvegicus) in China. Therefore, we aimed to examine the prevalence of Trichinella sp. infection in farmed minks in Weihai city, Shandong province, China and infer the possible route for Trichinella transmission to farmed American minks. In total, 289 muscle samples from minks and 102 carcasses of rats were collected from Weihai City. The appearance of Trichinella sp. was examined using the pooled artificial HCl-pepsin digestion method. The results showed that muscle larvae were detected in 20 of 289 minks (6.92%) and 2 of 102 synanthropic rats (1.96%). The larval density of Trichinella sp. in mink samples ranged from 0.025 to 0.815 larvae per gram (lpg), while the average larval burden in rats was 0.17 lpg. The isolates derived from minks and rats were identified at the species level using multiplex polymerase chain reaction (PCR), which revealed that the size of the two PCR products matched that of T. spiralis at 173 bp. Furthermore, sequence analysis showed 100% identity of the 5S rDNA inter-gene spacer regions of the two isolates to that of T. spiralis. This study presents a novel report of T. spiralis-mediated infection in minks and synanthropic rats in China. We highlight the vulnerability of farmed minks to Trichinella infection through exposure to synanthropic rats, which may raise a public health concern of potential zoonotic risks for domestic animals.

Constructing Mg2Co-Mg2CoH5 nano hydrogen pumps from LiCoO2 nanosheets for boosting the hydrogen storage property of MgH2.

Herein, an active positive electrode material, LiCoO2 nanosheets, was synthesized via a two-step method, which demonstrated a remarkable catalytic effect for the hydrogen storage property of MgH2. Incorporated with LiCoO2 nanosheets, MgH2 started to release hydrogen at 180 °C and a desorption content as high as 5.5 wt% H2 was attained within 60 min at 250 °C. The dehydrogenation activation energy was significantly decreased to 48.5 ± 0.4 kJ mol-1, achieving a 68.9% reduction compared to MgH2. It was verified by microstructural studies that Li+ served as an "anchor" to facilitate a uniform distribution of LiCoO2 "boat" among the MgH2 "ocean", benefitting the self-assembly of numerous Mg2Co-Mg2CoH5 couples on the surface of MgH2 during the cycling process. Meanwhile, the in situ formed Mg2Co-Mg2CoH5 couples were not restricted to offering multiple channels for fast hydrogen diffusion but also worked as "nano hydrogen pumps" to accelerate Mg/MgH2 hydrogen charging and discharging. This study provides an interesting example of effective cooperation between Li+ and Co3+ on improving the catalytic action toward MgH2. It shall shed light on efficient designing of high-efficient catalysts in hydrogen storage areas or other energy-related fields.

Celastrol inhibits lung cancer growth by triggering histone acetylation and acting synergically with HDAC inhibitors.

Alterations in histone modification have been linked to cancer development and progression. Celastrol, a Chinese herbal compound, shows potent anti-tumor effects through multiple signaling pathways. However, the involvement of histone modifications in this process has not yet been illustrated. In this study, barcode sequencing of a eukaryotic genome-wide deletion library revealed that histone modifications, especially histone acetylation associated with the NuA4 histone acetyltransferase complex, were involved in the anti-proliferation actions of celastrol. The essential roles of histone modification were verified by celastrol sensitivity tests in cells lacking specific genes, such as genes encoding the subunits of the NuA4 and Swr1 complex. The combination of celastrol and histone deacetylase inhibitors (HDACi), rather than the combination of celastrol and histone acetyltransferase inhibitors, synergistically suppressed cancer cell proliferation. In addition to upregulating H4K16 acetylation (H4K16ac), celastrol regulates H3K4 tri-methylation and H3S10 phosphorylation. Celastrol treatment significantly enhanced the suppressive effects of HDACi on lung cancer cell allografts in mice, with significant H4K16ac upregulation, indicating that a combination of celastrol and HDACi is a potential novel therapeutic approach for patients with lung cancer.

Encapsulation of Salmonella phage SL01 in alginate/carrageenan microcapsules as a delivery system and its application in vitro.

Phages can be used successfully to treat pathogenic bacteria including zoonotic pathogens that colonize the intestines of animals and humans. However, low pH and digestive enzyme activity under harsh gastric conditions affect phage viability, thereby reducing their effectiveness. In this study, alginate (ALG)/κ-carrageenan (CG) microcapsules were developed to encapsulate and release phage under simulated gastrointestinal conditions. The effects of ALG and CG concentrations on the encapsulation and loading efficiency of microcapsules, as well as the release behavior and antibacterial effects of microcapsules in simulating human intestinal pH and temperature, were investigated. Based on various indicators, when the concentration of ALG and CG were 2.0 and 0.3%, respectively, the obtained microcapsules have high encapsulation efficiency, strong protection, and high release efficiency in simulated intestinal fluid. This effect is attributed to the formation of a more tightly packed biopolymer network within the composite microcapsules based on the measurements of their microstructure properties. Bead-encapsulation is a promising, reliable, and cost-effective method for the functional delivery of phage targeting intestinal bacteria.

Benefits and Risks Associated with Low-Dose Aspirin Use for the Primary Prevention of Cardiovascular Disease: A Systematic Review and Meta-Analysis of Randomized Control Trials and Trial Sequential Analysis.

BACKGROUND: The role of aspirin in cardiovascular primary prevention remains controversial. Moreover, evidence for the potential benefits of aspirin in patients with high cardiovascular risk remains limited. OBJECTIVE: The aim of this study was to explore the role of low-dose aspirin in primary prevention. METHODS: The PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov databases were searched for randomized clinical trials (RCTs) from the date of inception to August 2021. The efficacy outcomes were major adverse cardiovascular events (MACE), myocardial infarction (MI), ischemic stroke (IS), all-cause mortality, and cardiovascular mortality, whereas safety outcomes were major bleeding, intracranial hemorrhage, and gastrointestinal (GI) bleeding. Subgroup analyses were based on different cardiovascular risks and diabetes statuses. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using the fixed- and random-effects models, and trial sequential analysis (TSA) was conducted to determine the robustness of the results. RESULTS: A total of 10 RCTs fulfilled the inclusion criteria. The use of aspirin was associated with a significant reduction in the risk of MACE (RR 0.89, 95% CI 0.84-0.93), MI (RR 0.86, 95% CI 0.78-0.95), and IS (RR 0.84, 95% CI 0.76-0.93); however, aspirin also increased the risk of safety outcomes, i.e. major bleeding (RR 1.42, 95% CI 1.26-1.60), intracranial hemorrhage (RR 1.33, 95% CI 1.11-1.59), and GI bleeding (RR 1.91, 95% CI 1.44-2.54). Subgroup analyses revealed that in the absence of a statistically significant interaction, a trend toward a net benefit of lower incidence of cardiovascular events (number needed to treat of MACE: high risk: 682 vs. low risk: 2191) and lesser risk of bleeding events (number needed to harm of major bleeding: high risk: 983 vs. low risk: 819) was seen in the subgroup of high cardiovascular risk. Meanwhile, the greater MACE reduction was also detected in the high-risk group of diabetes or nondiabetes patients. Furthermore, a post hoc subgroup analysis indicated a significant rate reduction in patients aged ≤ 70 years but not in patients aged > 70 years. TSA confirmed the benefit of aspirin for MACE up to a relative risk reduction of 10%. CONCLUSION: The current study demonstrated that the cardiovascular benefits of low-dose aspirin were equally balanced by major bleeding events. In addition, the potential beneficial effects might be seen in the population ≤ 70 years of age with high cardiovascular risk and no increased risk of bleeding.

Diabetic kidney disease-predisposing proinflammatory and profibrotic genes identified by weighted gene co-expression network analysis (WGCNA).

Diabetic kidney disease (DKD) is one of the most serious microvascular complications of diabetes. Despite enormous efforts, the underlying underpinnings of DKD remain incompletely appreciated. We sought to perform novel and informative bioinformatic analysis to explore the molecular mechanism of DKD. The gene expression profiles of GSE142025, GSE30528, and GSE30529 datasets were downloaded from the Gene Expression Omnibus database. After the GSE142025 data set was preprocessed, a gene co-expression network was constructed by weighted gene co-expression network analysis (WGCNA), and hub genes were selected in the key modules. Meanwhile, differentially expressed genes (DEGs) upregulated commonly were identified between the GSE30528 and GSE30529 datasets. Then, pathway and process enrichment analysis were performed for hub genes and commonly upregulated DEGs. Next, candidate targets were identified by comparing hub genes to commonly upregulated DEGs. Finally, reverse-transcription quantitative polymerase chain reaction (RT-qPCR) was carried out to validate the expression of candidate targets, and protein-protein interaction (PPI) network was constructed. A total of 17 modules were clustered by WGCNA, and the most significant turquoise module was selected. Based upon MM > 0.7 and GM > 0.7, 313 hub genes were screened out in turquoise module. Functional analysis of these 313 genes demonstrated their enrichment in pathways involved in leukocyte differentiation, cell morphogenesis, lymphocyte activation, vascular development, collagen synthesis, chemotaxis, and chemokine signaling. A total of 115 commonly upregulated DEGs were identified between the GSE30528 and GSE30529 datasets. Intriguingly, a total of six proinflammatory and profibrotic candidate targets were selected and validated in DKD mice in vivo, including CCR2, MOXD1, COL6A3, COL1A2, PYCARD, and C7. Based on WGCNA and DEG analysis of DKD datasets, six DKD-predisposing candidate targets were uncovered. The data suggest that inflammation and fibrosis are key mechanisms of DKD, and future studies may determine the causal link between the six proinflammatory and profibrotic genes and DKD.

Protein phase separation and its role in chromatin organization and diseases.

In the physical sciences, solid, liquid, and gas are the most familiar phase states, whose essence is their existence reflecting the different spatial distribution of molecular components. The biological molecules in the living cell also have differences in spatial distribution. The molecules organized in the form of membrane-bound organelles are well recognized. However, the biomolecules organized in membraneless compartments called biomolecular condensates remain elusive. The liquid-liquid phase separation (LLPS), as a new emerging scientific breakthrough, describes the biomolecules assembled in special distribution and appeared as membraneless condensates in the form of a new "phase" compared with the surrounding liquid milieu. LLPS provides an important theoretical basis for explaining the composition of biological molecules and related biological reactions. Mounting evidence has emerged recently that phase-separated condensates participate in various biological activities. This article reviews the occurrence of LLPS and underlying regulatory mechanisms for understanding how multivalent molecules drive phase transitions to form the biomolecular condensates. And, it also summarizes recent major progress in elucidating the roles of LLPS in chromatin organization and provides clues for the development of new innovative therapeutic strategies for related diseases.

Ferroptosis and its emerging role in tumor.

Ferroptosis is a novel form of programmed cell death characterized by iron-dependent lipid peroxidation accumulation. It is morphologically, biochemically, and genetically distinct from other known cell death, such as apoptosis, necrosis, and pyroptosis. Its regulatory mechanisms include iron metabolism, fatty acid metabolism, mitochondrial respiration, and antioxidative systems eliminating lipid peroxidation, such as glutathione synthesis, selenium-dependent glutathione peroxidase 4, and ubiquinone. The disruption of cellular redox systems causes damage to the cellular membrane leading to ferroptotic cell death. Recent studies have shown that numerous pathological diseases, like tumors, neurodegenerative disorders, and ischemia-reperfusion injury are associated with ferroptosis. As such, pharmacological regulation of ferroptosis either by activation or by suppression will provide a vast potential for treatments of relevant diseases. This review will discuss the advanced progress in ferroptosis and its regulatory mechanisms from both the antioxidative and oxidative sides. In addition, the roles of ferroptosis in various tumorigenesis, development, and therapeutic strategies will be addressed, particularly to chemotherapy and immunotherapy, as well as the discoveries from Traditional Chinese Medicine. This review will lead us to have a comprehensive understanding of the future exploration of ferroptosis and cancer therapy.

Electro-Acupuncture Attenuates Chronic Stress Responses via Up-Regulated Central NPY and GABA A Receptors in Rats.

Stress can increase the release of corticotropin-releasing factor (CRF) in the hypothalamus, resulting in attenuation of gastric motor functions. In contrast, central neuropeptide Y (NPY) can reduce the biological actions of CRF, and in turn weaken stress responses. Although electroacupuncture (EA) at stomach 36 (ST-36) has been shown to have anti-stress effects, its mechanism has not yet been investigated. The effect of EA at ST-36 on the hypothalamus-pituitary-adrenal (HPA) axis and gastrointestinal motility in chronic complicated stress (CCS) conditions have not been studied and the inhibitory mechanism of NPY on CRF through the gamma-aminobutyric acid (GABA) A receptor need to be further investigated. A CCS rat model was set up, EA at ST-36 was applied to the bilateral hind limbs every day prior to the stress loading. Further, a GABA A receptor antagonist was intracerebroventricularly (ICV) injected daily. Central CRF and NPY expression levels were studied, serum corticosterone and NPY concentrations were analyzed, and gastric motor functions were assessed. CCS rats showed significantly elevated CRF expression and corticosterone levels, which resulted in inhibited gastric motor functions. EA at ST-36 significantly increased central NPY mRNA expression and reduced central CRF mRNA expression as well as the plasma corticosterone level, helping to restore gastric motor function. However, ICV administration of the GABA A receptor antagonist significantly abolished these effects. EA at ST-36 upregulates the hypothalamic NPY system. NPY may, through the GABA A receptor, significantly antagonize the overexpressed central CRF and attenuate the HPA axis activities in CCS conditions, exerting influences and helping to restore gastric motor function.

Intranasal Administration of Oxytocin Attenuates Stress Responses Following Chronic Complicated Stress in Rats.

BACKGROUND/AIMS: Gastrointestinal (GI) symptoms may develop when we fail to adapt to various stressors of our daily life. Central oxytocin (OXT) can counteract the biological actions of corticotropin-releasing factor (CRF), and in turn attenuates stress responses. Administration (intracerebroventricular) of OXT significantly antagonized the inhibitory effects of chronic complicated stress (CCS) on GI dysmotility in rats. However, intracerebroventricular administration is an invasive pathway. Intranasal administration can rapidly deliver peptides to the brain avoiding stress response. The effects of intranasal OXT on hypothalamus-pituitary-adrenal axis and GI motility in CCS conditions have not been investigated. METHODS: A CCS rat model was set up, OXT 5, 10, or 20 µg were intranasal administered, 30 minutes prior to stress loading. Central CRF and OXT expression levels were analyzed, serum corticosterone and OXT concentrations were measured, and gastric and colonic motor functions were evaluated by gastric emptying, fecal pellet output, and motility recording system. RESULTS: Rats in CCS condition showed significantly increased CRF expression and corticosterone concentration, which resulted in delayed gastric emptying and increased fecal pellet output, attenuated gastric motility and enhanced colonic motility were also recorded. OXT 10 µg or 20 µg significantly reduced CRF mRNA expression and the corticosterone concentration, OXT 20 µg also helped to restore GI motor dysfunction induced by CCS. CONCLUSION: Intranasal administration of OXT has an anxiolytic effect and attenuates the hypothalamus-pituitary-adrenal axis in response to CCS, and gave effects which helped to restore GI dysmotility, and might be a new approach for the treatment of stress-induced GI motility disorders.

Early Detection of Toxoplasma gondii Infection In Mongolian Gerbil By Quantitative Real-Time PCR.

Toxoplasmosis, caused by Toxoplasma gondii, is associated with several clinical syndromes, including encephalitis, chorioretinitis, and congenital infection. Toxoplasma gondii is a ubiquitous apicomplexan parasite found in both humans and animals. Mongolian gerbils, which are more susceptible to both high- and low-virulence Toxoplasma strains compared with mice, are considered useful models for assessing diagnosis and treatment methods for toxoplasmosis, as well as infection by and host defense to this organism. Here we established a quantitative real-time polymerase chain reaction (qPCR) method targeting the B1 gene for early and specific detection of T. gondii infection in Mongolian gerbil. The detection limit of the developed qPCR was approximately 1 T. gondii tachyzoite. This method was also applied to detect T. gondii genomic DNA in experimentally infected Mongolian gerbils, with positive results in blood (66.7%), liver (73.3%), lung (80.0%), spleen (80.0%), and peritoneal fluid (66.7%) samples as early as 1 day postinfection. Specificity tests confirmed no cross-reactivity with DNA templates of Neospora caninum, Cryptosporidium parvum, Eimeria tenella, Trypanosoma evansi, Schistosoma japonicum, Angiostrongylus cantonensis, and Strongyloides stercoralis. This study first reports the use of Mongolian gerbils as an animal model for early diagnosis of toxoplasmosis by qPCR.