Circulating extracellular vesicles as novel biomarkers for pulmonary arterial hypertension in patients with systemic lupus erythematosus.

Introduction: Pulmonary arterial hypertension (PAH) is a serious complication of systemic lupus erythematosus (SLE) with increased mortality. A prothrombotic state may contribute to pathogenesis of SLE-PAH. Extracellular vesicles (EVs) are known to be associated with thrombosis. Here, we investigated circulating EVs and their associations with SLE-PAH. Methods: Eighteen SLE-PAH patients, 36 SLE-non-PAH patients, and 36 healthy controls (HCs) were enrolled. Flow cytometry was used to analyze circulating EVs from leukocytes (LEVs), red blood cells (REVs), platelets (PEVs), endothelial cells (EEVs), and Annexin V+ EVs with membrane phosphatidylserine (PS) exposure. Results: Plasma levels of all EV subgroups were elevated in SLE patients with or without PAH compared to HCs. Furthermore, plasma Annexin V+ EVs, LEVs, PEVs, REVs, EEVs, and Annexin V+ REVs were significantly elevated in SLE-PAH patients compared to SLE-non-PAH patients. Additionally, PAH patients with moderate/high SLE showed a significant increase in LEVs, PEVs, REVs, Annexin V+ EVs, and Annexin V+ REVs compared to SLE-non-PAH patients. However, PAH patients with inactive/mild SLE only exhibited elevations in Annexin V+ EVs, REVs, and Annexin V+ REVs. In the SLE-PAH patients, EEVs were positively correlated with pulmonary arterial systolic pressure, while PEVs and EEVs were positively correlated with right ventricular diameter. Moreover, the receiver operating characteristic curve indicated that Annexin V+ EVs, LEVs, PEVs, REVs, EEVs and Annexin V+ REVs could predict the presence of PAH in SLE patients. Importantly, multivariate logistic regression analysis showed that circulating levels of LEVs or REVs, anti-nRNP antibody, and serositis were independent risk factors for PAH in SLE patients. Discussion: Findings reveal that specific subgroups of circulating EVs contribute to the hypercoagulation state and the severity of SLE-PAH. Higher plasma levels of LEVs or REVs may serve as biomarkers for SLE-PAH.

Metal nanoparticles encapsulation within multi-shell spongy-core porous microspheres for efficient tandem catalysis.

The "one-pot" cascade process involves multiple catalytic conversions followed by a single workup stage. This method has the capability to optimize catalytic efficiency by reducing chemical processes. The key to achieving cascade reactions lies in designing cascade catalysts with well-dispersed, stably immobilized, and accessible noble metal nanoparticles for multiple catalytic conversions. This work presents a strategy for creating long-lasting cascade catalysts by encapsulating Ru and Pd nanoparticles within multi-shell spongy-core porous microspheres (MS-SC-PMs). This cascade catalyst strategy enables the continuous hydrogenation of nitrobenzene to aniline and further to cyclohexylamine, demonstrating both high selectivity and conversion rates. Notably, this approach overcomes the typical challenges associated with noble metal nanoparticles, such as poor stability and recyclability, as it maintains its performance over ten consecutive cycles. Additionally, the MS-SC-PMs have the versatility to encapsulate various metal nanoparticles, providing catalytic versatility, scalability, and a promising avenue for designing long-lasting catalysts loaded with nanoparticles.

Breast cancer with cervix, lung and neck metastases: a case report and literature review.

Background: Breast cancer has the potential to metastasize to various sites; however, cases of metastasis to the cervix are rare. Here, we present clinical and pathological data from a rare case of primary breast cancer metastasis to the cervix, including imaging characteristics and clinical progression. Case Description: A 68-year-old female patient self-detected nodules in her right breast. B-ultrasound examination revealed multiple nodules in the right breast, classified as Breast Imaging Reporting and Data System (BI-RADS) 4c. Radical treatment for right breast cancer was commenced. Histopathologic diagnosis revealed invasive ductal breast carcinoma of no specific type, with intraductal carcinoma in the right breast. Immunohistochemical analysis indicated that the tumor was androgen receptor (AR)-diffuse strong positive, estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, with human epidermal receptor-2 (HER2, c-erbB-2) overexpression, and Ki-67 proliferation index 60%. The tumor was positive for GATA binding protein 3 (GATA-3) and fluorescence in situ hybridization (FISH) analysis revealed HER2 gene amplification. Chemotherapy was discontinued after completing three cycles. Three years after stopping chemotherapy, she experienced lower abdominal, pain with cervical bleeding, and underwent aspiration biopsy. Immunohistochemical results indicated: AR-diffuse strong positive, ER-negative, PR-negative, c-erbB-2-negative, and Ki-67 30%, with gross cystic disease fluid protein-15 (GCDFP-15) and GATA-3 both diffuse strong positive. Lung mass detection prompted lung puncture and biopsy, with immunohistochemical results: ER-negative, PR-negative, c-erbB-2-positive, Ki-67 30%, with GCDFP-15-diffuse positive, and GATA-3-diffuse positive. No HER2 gene amplification was detected by FISH. She was diagnosed with ductal breast carcinoma metastasized to the uterus and lung, based on morphological, immunohistochemical, and clinical findings. Eight months later, she developed a neck mass, and mass puncture and biopsy confirmed metastatic breast cancer [immunohistochemical results: ER-negative, PR-negative, c-erbB-2-positive, Ki-67 30%, trichorhinophalangeal syndrome type 1 (TRPS1)-positive, and GATA-3-positive]. The primary tumor was ER-negative, PR-negative, with HER2 amplification. Later, cervical, pulmonary, and neck metastases were ER-negative, PR-negative, and HER2 negative. The patient remains alive; last follow-up was February 15, 2024, 50 months after radical treatment for breast cancer. Conclusions: We report a relatively rare case of primary breast cancer metastasis to three metastatic sites: cervix, lung, and neck. To our best knowledge, this is the first report of primary breast cancer metastasis to three sites including the cervix.

Noninvasive Therapies: A Forthcoming Approach to Parkinson's Treatment.

In this review, we have discussed the invasive and non-invasive treatment options for Parkinson's Disease (PD) following their safety, specificity, and reliability. Initially, this study has highlighted the invasive treatment options and the side effects they possess. A deep understanding of L-Dopa treatment, as oral or infusion, and the use of dopamine agonists has indicated that there is a need to acquire an alternative treatment for PD. The combined therapy with L-Dopa has been proven to affect PD, but with some limitations, such as mild to chronic side effects, with particular requirements of age and health of the patient and a large amount of expenditure. In the discussion of noninvasive methods to treat PD, we have found that this approach is comparatively slow and requires repetitive sessions, but is safe, effective, and reliable at any stage of PD. Electroconvulsive therapy has revealed its effectiveness in various neurological diseases, including PD. Transcranial current stimulation (direct or alternative) has already been shown to have an alleviative response to PD symptoms. Transcranial magnetic stimulations and other strategies of using the magnetic field for potential treatment options for PD need to be explored further imminently.

TUBB4A Inhibits Glioma Development by Regulating ROS-PINK1/Parkin-Mitophagy Pathway.

Glioma is a refractory malignant tumor with a powerful capacity for invasiveness and a poor prognosis. This study aims to investigate the role and mechanism of tubulin beta class IVA (TUBB4A) in glioma progression. The differential expression of TUBB4A in humans was obtained from databases and analyzed. Glioma cells U251-MG and U87-MG were intervened by pcDNA3.1(+) and TUBB4A overexpression plasmid. MTT, CCK8, LDH, wound healing, transwell, and western blotting were used to explore whether TUBB4A participates in the development of glioma. Reactive oxygen species (ROS) were detected by the DCFH-DA probe. Mitochondrial membrane potential (MMP) was examined by JC-1. It was found that TUBB4A expression level correlated with tumor grade, IDH1 status, 1p/19q status, and poor survival in glioma patients. In addition, TUBB4A overexpression inhibited the proliferation, migration, and invasion of U251-MG and U87-MG, while increasing the degree of apoptosis. Notably, TUBB4A overexpression promotes ROS generation and MMP depolarization, and induces mitophagy through the PINK1/Parkin pathway. Interestingly, mitochondria-targeted ROS scavenger reversed the effect of TUBB4A overexpression on PINK1/Parkin expression and mitophagy, whereas mitophagy inhibitor did not affect ROS production. And the effect of TUBB4A overexpression on mitophagy and glioma progression was consistent with that of PINK1/Parkin agonist. In conclusion, TUBB4A is a molecular marker for predicting the prognosis of glioma patients and an effective target for inhibiting glioma progression by regulating ROS-PINK1/Parkin-mitophagy pathway.

Forskolin improves experimental autoimmune encephalomyelitis in mice probably by inhibiting the calcium and the IL-17-STEAP4 signaling pathway.

Multiple sclerosis (MS) is a chronic autoimmune disease in the central nervous system. Forskolin (FSK) is a plant-derived diterpene with excellent immunomodulatory properties and has not been systematically reported for treating MS. This study investigated the therapeutic effects of FSK on cellular and animal MS models and preliminarily explored related mechanisms. The results showed that FSK suppressed the inflammatory response, reduced the expression of STEAP4, and relieved iron deposition in BV-2 cells pretreated by LPS at the cellular level. Meanwhile, at the animal level, FSK treatment halted the progression of experimental autoimmune encephalomyelitis (EAE), alleviated the damage at the lesion sites, reduced the concentration of proinflammatory factors in peripheral blood, and inhibited the immune response of peripheral immune organs in EAE mice. Besides, FSK treatment decreased the expression of STEAP4 in the spinal cord and effectively restored the iron balance in the brain, spinal cord, and serum of EAE mice. Further investigation showed that FSK can reduce IL-17 expression, prevent the differentiation of TH17 cells, and inhibit the calcium signaling pathway. Thus, these results demonstrate that FSK may have the potential to treat MS clinically.

State transition learning with limited data for safe control of switched nonlinear systems.

Switching dynamics are prevalent in real-world systems, arising from either intrinsic changes or responses to external influences, which can be appropriately modeled by switched systems. Control synthesis for switched systems, especially integrating safety constraints, is recognized as a significant and challenging topic. This study focuses on devising a learning-based control strategy for switched nonlinear systems operating under arbitrary switching law. It aims to maintain stability and uphold safety constraints despite limited system data. To achieve these goals, we employ the control barrier function method and Lyapunov theory to synthesize a controller that delivers both safety and stability performance. To overcome the difficulties associated with constructing the specific control barrier and Lyapunov function and take advantage of switching characteristics, we create a neural control barrier function and a neural Lyapunov function separately for control policies through a state transition learning approach. These neural barrier and Lyapunov functions facilitate the design of the safe controller. The corresponding control policy is governed by learning from two components: policy loss and forward state estimation. The effectiveness of the developing scheme is verified through simulation examples.

Genomes of autotetraploid wild and cultivated Ziziphus mauritiana reveal polyploid evolution and crop domestication.

Indian jujube (Ziziphus mauritiana) holds a prominent position in the global fruit and pharmaceutical markets. Here, we report the assemblies of haplotype-resolved, telomere-to-telomere genomes of autotetraploid wild and cultivated Indian jujube plants using a two-stage assembly strategy. The generation of these genomes permitted in-depth investigations into the divergence and evolutionary history of this important fruit crop. Using a graph-based pan-genome constructed from eight monoploid genomes, we identified structural variation (SV)-FST hotspots and SV hotspots. Gap-free genomes provide a means to obtain a global view of centromere structures. We identified presence-absence variation-related genes in four monoploid genomes (cI, cIII, wI, and wIII) and resequencing populations. We also present the population structure and domestication trajectory of the Indian jujube based on the resequencing of 73 wild and cultivated accessions. Metabolomic and transcriptomic analyses of mature fruits of wild and cultivated accessions unveiled the genetic basis underlying loss of fruit astringency during domestication of Indian jujube. This study reveals mechanisms underlying the divergence, evolution, and domestication of the autotetraploid Indian jujube and provides rich and reliable genetic resources for future research.

Construction of Recombinant Marek's Disease Virus Co-Expressing VP1 and VP2 of Chicken Infectious Anemia Virus.

The chicken infectious anemia virus (CIAV) has been reported in major poultry-producing countries and poses a significant threat to the poultry industry worldwide. In this study, two Marek's disease virus (MDV) recombinants, rMDV-CIAV-1 and rMDV-CIAV-2, were generated by inserting the CIAV VP1 and VP2 genes into the MDV vaccine strain 814 at the US2 site using the fosmid-based rescue system. For rMDV-CIAV-1, an internal ribosome entry site was inserted between VP1 and VP2, so that both proteins were produced from a single open reading frame. In rMDV-CIAV-2, VP1 and VP2 were cloned into different open reading frames and inserted into the MDV genome. The recombinant viruses simultaneously expressed VP1 and VP2 in infected chicken embryo fibroblasts and exhibited growth kinetics similar to those of the parent MDV. The two recombinant viruses induced antibodies against CIAV in chickens. A single dose of the recombinant viruses provided strong protection against CIAV-induced anemia in chickens. These recombinant VP1- and VP2-expressing MDVs are potential vaccines against CIAV in chickens.

Serum ECM1 is a promising biomarker for staging and monitoring fibrosis in patients with chronic hepatitis B.

It is critical to assess the extent and progression of liver fibrosis for patients to receive suitable treatments, but its diagnostic methods remain unmet. Extracellular matrix protein 1 (ECM1) has previously been reported to be a key factor in the induction and progression of liver fibrosis. However, little is known about the use of ECM1 as a biomarker to evaluate fibrosis. In a CCl4-induced mouse model of liver fibrosis, the present study demonstrated that ECM1 decreased with gradually increasing fibrosis. Using biopsy as a reference, the serum ECM1 levels decreased with increasing fibrosis stage in 247 patients with liver fibrosis, but there were no significant changes between fibrosis stage 2 and stage 0-1. To improve the performance of ECM1, age, platelet count, and ECM1 concentration were combined to calculate an EPA (ECM1-platelet-age) score (ranging from 0 to 10). The areas under the receiver operating characteristic curve of the EPA scores for the detection of F⩾2, F⩾3, and F4 were 0.6801, 0.7377, and 0.8083, respectively, which showed a comparable or significantly greater diagnostic performance for assessing fibrosis than that of the AST/ALT ratio, APRI score, or FIB-4 score. In HBV patients following antiviral treatment, the dynamics of the EPA score depended on the status of liver fibrosis development. The accuracy of the EPA score in predicting fibrosis regression and progression was 66.00% and 71.43%, respectively, while that of the LSM, another useful method for monitoring hepatic fibrosis changes during treatment, was only 52.00% and 7.14%, respectively. Compared with healthy controls, there were lower levels of serum ECM1 in HBV patients and individuals with HCV infection, MAFLD, ALD, PBC, and DILI. These findings suggested that individuals with reduced ECM1 levels may have a risk of developing liver injury, and further examinations or medical care are needed. In conclusion, the ECM1-containing EPA score is a valuable noninvasive test for staging fibrosis and predicting the progression of liver fibrosis. Additionally, ECM1 alone is an indicator for distinguishing patients with liver injury from healthy controls.

Multifunctional honeysuckle extract/attapulgite/chitosan composite films containing natural carbon dots for intelligent food packaging.

In order to fulfill people's requirements for food quality and safety, it is a promising strategy to develop intelligent biodegradable food packaging materials. Herein, honeysuckle extracts/attapulgite/chitosan composite films containing natural carbon dots were fabricated for intelligent food packaging. Different characterization techniques were employed to study the obtained composite films, while the physicochemical properties, optical properties, antibacterial and antioxidant activities of composite films were determined. The obtained composite films presented good mechanical, antibacterial and antioxidant properties, and the antibacterial ratios of composite films against Escherichia coli and Staphylococcus aureus were 99.27 ± 0.18 % and 98.85 ± 0.65 %, respectively. When the added amount of honeysuckle extracts/attapulgite nanocomposites was 4.76 %, the tensile strength and elongation at break of composite films reached 24.9 ± 2.35 MPa and 64.8 ± 2.11 %, respectively, which were obviously higher than that of pure chitosan film. Furthermore, the composite films exhibited excellent UV shielding and blue fluorescence properties, as well as pH-sensitivity due to the presence of caffeoquinic acid-based natural carbon dots derived from honeysuckle extract. Therefore, the composite films indicated a potential application for intelligent food packaging.

A novel triple-signal biosensor based on ZrFe-MOF@PtNPs for ultrasensitive aflatoxins detection.

The development of more sensitive, stable, and portable biosensors is crucial for meeting the growing demands of diverse and complex detection environments. MOF-based nanozymes have emerged as excellent optical reporters, making them ideal signal donors for constructing multi-signal lateral flow immunoassays (LFIA). In this study, a ZrFe-MOF@PtNPs nanocomposite was synthesized by uniformly depositing platinum nanoparticles (PtNPs) onto the surface of ZrFe-MOFs using an impregnation-reduction method. The ZrFe-MOF@PtNPs exhibited broad absorption spectra, excellent peroxidase-like activity (SA = 21.77 U/mg), high solvent stability, and efficient antibody binding capability. A portable LFIA platform was developed based on ZrFe-MOF@PtNPs and a smartphone for the targeted detection of carcinogenic aflatoxins. This method enabled the readout of colorimetric, fluorescent, and catalytic signals, significantly enhancing detection sensitivity, ensuring result accuracy, and expanding the dynamic detection range. For aflatoxin M1, the calculation of the detection limit of the three signal modes reached as low as 0.0062 ng/mL, which is two orders of magnitude more sensitive than AuNPs-LFIA (0.1839 ng/mL). This study provides effective guidance for multifunctional modification of MOFs and serves as a reference for the application of MOF-based nanozymes in point-of-care biosensors.

Construction of recombinant Marek's disease virus co-expressing σB and σC of avian reoviruses.

Avian reoviruses (ARVs) cause viral arthritis or tenosynovitis, resulting in poor weight gain and increased feed conversion ratios in chickens. In this study, we generated three Marek's disease virus (MDV) recombinants, namely, rMDV-ARV-σB, rMDV-ARV-σC, and rMDV-ARV-σB + C, expressing ARV σB, σC, and both σB and σC, respectively. In rMDV-ARV-σB and rMDV-ARV-σC, the σB or σC gene was inserted into the US2 gene of MDV vaccine strain 814 using a fosmid-based rescue system. In rMDV-ARV-σB + C, the σB and σC genes were cloned into different expression cassettes, which were co-inserted into the US2 gene of the MDV 814 strain. In infected chicken embryo fibroblasts (CEFs), the recombinant virus rMDV-ARV-σB expressed σB, rMDV-ARV-σC expressed σC, and the rMDV-ARV-σB + C virus simultaneously expressed σB and σC. These recombinant viruses exhibited growth kinetics in CEFs similar to those of the parent MDV, and the inserted genes were stably maintained and expressed in the recombinant MDVs after 20 passages in cell cultures. These recombinant MDVs expressing σB and σC will provide potential vaccines against ARV infection in chickens.

Study of the uptake mechanism of two small extracellular vesicle subtypes by granulosa cells.

As a new mechanism of intercellular communication, the uptake of extracellular vesicles (EVs) by receptor cells has become a hot topic in the field. Previously, research on the uptake of EVs has focused on the mechanism of small EVs (sEVs, also known as exosomes). As sEVs represent a mixed heterogeneous population, the issue of whether there are different uptake mechanisms for different subsets of sEVs by recipient cells urgently need to be addressed. There are EVs in follicular fluid, which play an important role in the communication between follicular cells and the development of oocytes. Previously, we isolated two subtypes of sEVs in follicular fluid: low density-sEVs (LD-sEVs) and high density-sEVs (HD-sEVs). The current study aimed to explore the uptake characteristics of these two subtypes of sEVs by granulosa cells. First, PKH67 was used to label the two sEVs subtypes, and we observed their uptake by granulosa cells using confocal microscopy and flow cytometry. We then explored the specific mechanisms underlying uptake of these two sEV subtypes by granulosa cells using specific inhibitors and RNA interference. The results showed that granulosa cells took up both kinds of sEVs through a clathrin-independent pathway. In addition to requiring caveolin, cholesterol, and Na+/H+ exchange, the uptake of HD-sEVs also depended on the activity of tyrosine kinase and phosphoinositide 3-kinase. A better understanding of the mechanism of granulosa cell uptake of different subtypes of sEVs in follicular fluid is of considerable significance leading to more accurate use of EVs for targeted treatment of infertility and other related diseases.

Customized T-time inner sampling network with uncertainty-aware data augmentation strategy for multi-annotated lesion segmentation.

Segmentation in medical images is inherently ambiguous. It is crucial to capture the uncertainty in lesion segmentations to assist cancer diagnosis and further interventions. Recent works have made great progress in generating multiple plausible segmentation results as diversified references to account for the uncertainty in lesion segmentations. However, the efficiency of existing models is limited, and the uncertainty information lying in multi-annotated datasets remains to be fully utilized. In this study, we propose a series of methods to corporately deal with the above limitation and leverage the abundant information in multi-annotated datasets: (1) Customized T-time Inner Sampling Network to promote the modeling flexibility and efficiently generate samples matching the ground-truth distribution of a number of annotators; (2) Uncertainty Degree defined for quantitatively measuring the uncertainty of each sample and the imbalance of the whole multi-annotated dataset from a brand new perspective; (3) Uncertainty-aware Data Augmentation Strategy to help probabilistic models adaptively fit samples with different ranges of uncertainty. We have evaluated each of them on both the publicly available lung nodule dataset and our in-house Liver Tumor dataset. Results show that our proposed methods achieves the overall best performance on both accuracy and efficiency, demonstrating its great potential in lesion segmentations and more downstream tasks in real clinical scenarios.

System analysis based on weighted gene co-expression analysis identifies SOX7 as a novel regulator of hepatic stellate cell activation and liver fibrosis.

Hepatic stellate cell (HSC) activation is the essential pathological process of liver fibrosis (LF). The molecular mechanisms regulating HSC activation and LF are incompletely understood. Here, we explored the effect of transcription factor SRY-related high mobility group box 7 (SOX7) on HSC activation and LF, and the underlying molecular mechanism. We found the expression levels of SOX7 were decreased in human and mouse fibrotic livers, particularly at the fibrotic foci. SOX7 was also downregulated in primary activated HSCs and TGF-ß1 stimulated LX-2 cells. SOX7 knockdown promoted activation and proliferation of LX-2 cells while inhibiting their apoptosis. On the other hand, overexpression of SOX7 suppressed the activation and proliferation of HSCs. Mechanistically, SOX7 attenuates HSC activation and LF by decreasing the expression of ß-catenin and phosphorylation of Smad2 and Smad3 induced by TGF-ß1. Furthermore, overexpression of SOX7 using AAV8-SOX7 mouse models ameliorated the extent of LF in response to CCl4 treatment in vivo. Collectively, SOX7 suppressed HSC activation and LF. Targeting SOX7, therefore, could be a potential novel strategy to protect against LF.

Allantoin reduces glucotoxicity and lipotoxicity in a type 2 diabetes rat model by modulating the PI3K and MAPK signaling pathways.

Objective: The current study aimed to investigate the potential therapeutic impact of allantoin on diabetes produced by a high-fat diet (HFD) and streptozotocin (STZ) in rats. Subjects and methods: Male Sprague-Dawley rats were fed a high-fat diet to induce insulin resistance, followed by streptozotocin injection to induce diabetes. The effect of oral treatment of allantoin (200, 400 and 800 mg/kg/day) for 8 weeks was evaluated by calculating the alteration in metabolic parameters, biochemical indicators, the oral glucose tolerance tests (OGTT) and hyperinsulinemic-euglycemic clamp tests were performed. Histopathological studies were performed in the liver, kidney and pancreas. Next, the expressions of the MAPK and insulin signaling pathway were measured by Western blot analysis to elucidate the potential mechanism underlying these antidiabetic activities. Results: The administration of allantoin resulted in a significant decrease in fasting blood glucose (FBG) levels, glycogen levels, and glycosylated hemoglobin levels in diabetic rats. Additionally, allantoin therapy led to a dose-dependent increase in body weight growth and serum insulin levels. In addition, the administration of allantoin resulted in a considerable reduction in lipid profile levels and amelioration of histological alterations in rats with diabetes. The administration of allantoin to diabetic rats resulted in a notable decrease in Malondialdehyde (MDA) levels, accompanied by an increase in the activity of antioxidant enzymes in the serum, liver, and kidney. The findings of oral glucose tolerance and hyperinsulinemic-euglycemic clamp tests demonstrated a significant rise in insulin resistance following the administration of allantoin. The upregulation of IRS-2/PI3K/p-Akt/GLUT expression by allantoin suggests a mechanistic relationship between the PI3K/Akt signaling pathway and the antihyperglycemic activity of allantoin. Furthermore, it resulted in a reduction in the levels of TGF-ß1/p38MAPK/Caspase-3 expression in the aforementioned rat tissues affected by diabetes. Conclusions: This study implies that allantoin treats type 2 diabetes by activating PI3K. Additionally, it reduces liver, kidney, and pancreatic apoptosis and inflammation-induced insulin resistance.re.

Ligilactobacillus salivarius XP132 with antibacterial and immunomodulatory activities inhibits horizontal and vertical transmission of Salmonella Pullorum in chickens.

Probiotics are increasingly recognized for their capacity to combat pathogenic bacteria. In this study, we isolated a strain of Ligilactobacillus salivarius XP132 from the gut microbiota of healthy chickens. This strain exhibited resistance to low pH and bile salts, auto-aggregation capabilities, and the ability to co-aggregate with pathogenic Salmonella. The in vitro antibacterial activity of Ligilactobacillus salivarius XP132 was tested using an Oxford cup antibacterial test, and the results showed that Ligilactobacillus salivarius XP132 exhibited broad-spectrum antibacterial activity, with especially strong antibacterial activity against Salmonella. In animal experiments with white feather broilers and specific-pathogens-free (SPF) chickens, we orally administered 1 × 109 CFU XP132 live bacteria per chicken per day, and detected the content of Salmonella in the liver, spleen, intestinal contents, and eggs of the chickens by RT-qPCR. Oral administration of Lactobacillus salivarius XP132 group significantly reduced the levels of Salmonella in chicken liver, spleen, intestinal contents and eggs, and the oral administration of Ligilactobacillus salivarius XP132 significantly inhibited the horizontal and vertical transmission of Salmonella in SPF chickens and white-feathered broilers. After oral administration of XP132, the production of chicken serum anti-infective cytokine IFN-γ was also significantly up-regulated, thereby enhancing the host's ability to resist infection. In addition, the production of various serum inflammatory cytokines, including IL-1ß, IL-6, IL-8, and TNF-α, was down-regulated, leading to significant amelioration of the inflammatory response induced by S. Pullorum in chickens. These findings suggest that Ligilactobacillus salivarius XP132 possesses potent antibacterial and immunomodulatory properties that effectively prevent both horizontal and vertical transmission of Salmonella Pullorum, highlighting its potential as a valuable tool for the prevention and control of Salmonella disease.

Association between triglyceride to HDL cholesterol ratio and a risk of diabetes mellitus: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to investigate the link between the triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-C) and the occurrence of type 2 diabetes mellitus (T2DM). METHODS: PubMed, Embase, and Scopus databases were searched for cohort and case-control studies that reported on the link between TG/HDL-C and a risk of T2DM, with no restrictions on criteria used for the definition and categorization of low and high TG/HDL-C ratios. RESULTS: A total of 20 studies were included. There was considerable variability in terms of categorization of low or normal and higher TG/HDL-C ratio among the studies. Patients with high TG/HDL-C ratio had markedly higher risk of developing T2DM compared with patients with low or normal TG/HDL-C. Each unit increase in the ratio correlated with the increased risk of diabetes. Subgroup analysis based on sex showed an increased risk of T2DM in males and females with a high ratio compared with the group with a low/normal ratio. CONCLUSION: Higher TG/HDL-C ratio correlates with increased risk of T2DM. Despite limitations, the study demonstrates a possible value of using TG/HDL-C ratio as a biomarker for diabetes risk.

Bidirectional effects of the tryptophan metabolite indole-3-acetaldehyde on colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) has a high incidence and mortality. Recent studies have shown that indole derivatives involved in gut microbiota metabolism can impact the tumorigenesis, progression, and metastasis of CRC. AIM: To investigate the effect of indole-3-acetaldehyde (IAAD) on CRC. METHODS: The effect of IAAD was evaluated in a syngeneic mouse model of CRC and CRC cell lines (HCT116 and DLD-1). Cell proliferation was assessed by Ki-67 fluorescence staining and cytotoxicity tests. Cell apoptosis was analysed by flow cytometry after staining with Annexin V-fluorescein isothiocyanate and propidium iodide. Invasiveness was investigated using the transwell assay. Western blotting and real-time fluorescence quantitative polymerase chain reaction were performed to evaluate the expression of epithelial-mesenchymal transition related genes and aryl hydrocarbon receptor (AhR) downstream genes. The PharmMapper, SEA, and SWISS databases were used to screen for potential target proteins of IAAD, and the core proteins were identified through the String database. RESULTS: IAAD reduced tumorigenesis in a syngeneic mouse model. In CRC cell lines HCT116 and DLD1, IAAD exhibited cytotoxicity starting at 24 h of treatment, while it reduced Ki67 expression in the nucleus. The results of flow cytometry showed that IAAD induced apoptosis in HCT116 cells but had no effect on DLD1 cells, which may be related to the activation of AhR. IAAD can also increase the invasiveness and epithelial-mesenchymal transition of HCT116 and DLD1 cells. At low concentrations (< 12.5 µmol/L), IAAD only exhibited cytotoxic effects without promoting cell invasion. In addition, predictions based on online databases, protein-protein interaction analysis, and molecular docking showed that IAAD can bind to matrix metalloproteinase-9 (MMP9), angiotensin converting enzyme (ACE), poly(ADP-ribose) polymerase-1 (PARP1), matrix metalloproteinase-2 (MMP2), and myeloperoxidase (MPO). CONCLUSION: Indole-3-aldehyde can induce cell apoptosis and inhibit cell proliferation to prevent the occurrence of CRC; however, at high concentrations (≥ 25 µmol/L), it can also promote epithelial-mesenchymal transition and invasion in CRC cells. IAAD activates AhR and directly binds MMP9, ACE, PARP1, MMP2, and MPO, which partly reveals why it has a bidirectional effect.