Study on the immune-enhancing and inhabiting transmissible gastroenteritis virus effects of polysaccharides from Cimicifuga rhizoma.

Cimicifugae rhizoma is a traditional Chinese herbal medicine in China, and modern pharmacological research showed that it has obvious antiviral activity. Many polysaccharides have been proved to have immune enhancement and antiviral activity, but there are few studies on the biological activity of Cimicifuga rhizoma polysaccharide (CRP). The aim was to explore the character of CRP and its effects on improving immune activity and inhibiting transmissible gastroenteritis virus (TGEV). The monosaccharide composition, molecular weight, fourier transform infrared spectra and electron microscopy analysis of CRP was measured. The effect of CRP on immune activity in lymphocytes and RAW264.7 cells were studied by colorimetry, FITC-OVA fluorescent staining and ELISA. The effect of CRP on TGEV-infected PK-15 cells was determined using Real-time PCR, Hoechst fluorescence staining, trypan blue staining, acridine orange staining, Annexin V-FITC/PI fluorescent staining, DCFH-DA loading probe, and JC-1 staining. Network pharmacology was used to predict the targets of CRP in enhancing immunity and anti-TGEV, and molecular docking was used to further analyze the binding mode between CPR and core targets. The results showed that CRP was mainly composed of glucose and galactose, and its molecular weight was 64.28 kDa. The content of iNOS and NO in CRP group were significantly higher than the control group. CRP (125 and 62.5 µg/mL) could significantly enhance the phagocytic capacity of RAW264.7 cells, and imprive the content of IL-1ß content compared with control group. 250 µg/mL of CRP possessed the significant inhibitory effect on TGEV, which could significantly reduce the apoptosis compared to TGVE group and inhibit the decrease in mitochondrial membrane potential compared to TGVE group. The mRNA expression of TGEV N gene in CRP groups was significantly lower than TGEV group. PPI showed that the core targets of immune-enhancing were AKT1, MMP9, HSP90AA1, etc., and the core targets of TGE were CASP3, MMP9, EGFR, etc. Molecular docking show that CRP has binding potential with target. These results indicated that CRP possessed the better immune enhancement effect and anti-TGEV activity.

Effects of light perception on visual function recovery in patients with traumatic optic neuropathy.

This study aimed to assess the impact of light perception presence or absence on visual function recovery in patients with traumatic optic neuropathy (TON). A retrospective analysis was conducted on the clinical data of 206 TON patients. Based on the presence or absence of light perception after injury, patients were categorized into a light perception group and a non-light perception group. A comparison was made between the two groups regarding visual acuity recovery before and after treatment. The non-light perception group comprised 63 patients, with a treatment effectiveness rate of 39.68%. The light perception group consisted of 143 patients, with a treatment effectiveness rate of 74.83%. The difference between the two groups was statistically significant (χ2 = 23.464, P < 0.01). Subgroup analysis indicated that surgical treatment appeared to be more effective than steroid hormone therapy for patients with light perception. Conversely, for patients without light perception, there was no significant difference in the effectiveness of the two methods. The total effectiveness rate of the light perception group was significantly higher than that of the non-light perception group, suggesting that patients with light perception before treatment experience better outcomes compared to those without light perception. Treatment choices should be individualized to ensure optimal results.

Polygonum cillinerve polysaccharide inhibits transmissible gastroenteritis virus by regulating microRNA-181.

Transmissible gastroenteritis virus (TGEV) is an important pathogen capable of altering the expression profile of cellular miRNA. In this study, the potential of Polygonum cillinerve polysaccharide (PCP) to treat TGEV-infected piglets was evaluated through in vivo experiments. High-throughput sequencing technology was employed to identify 9 up-regulated and 17 down-regulated miRNAs during PCP-mediated inhibition of TGEV infection in PK15 cells. Additionally, miR-181 was found to be associated with target genes of key proteins in the apoptosis pathway. PK15 cells were treated with various concentrations of PCP following transfection with miR-181 mimic or inhibitor. Real-time PCR assessed the impact on TGEV replication, while electron microscopy (TEM) and Hoechst fluorescence staining evaluated cellular functionality. Western blot analysis was utilized to assess the expression of key signaling factors-cytochrome C (cyt C), caspase 9, and P53-in the apoptotic signaling pathway. The results showed that compared with the control group, 250 µg/mL PCP significantly inhibited TGEV gRNA replication and gene N expression (P < 0.01). Microscopic examination revealed uniform cell morphology and fewer floating cells in PCP-treated groups (250 and 125 µg/mL). TEM analysis showed no typical virus structure in the 250 µg/mL PCP group, and apoptosis staining indicated a significant reduction in apoptotic cells at this concentration. Furthermore, PCP may inhibit TGEV-induced apoptosis via the Caspase-dependent mitochondrial pathway following miR-181 transfection. These findings provide a theoretical basis for further exploration into the mechanism of PCP's anti-TGEV properties.

Optimization of adsorption performance of cerium-loaded intercalated bentonite by CCD-RSM and GA-BPNN and its application in simultaneous removal of phosphorus and ammonia nitrogen.

Excessive phosphorus (P) and ammonia nitrogen (NH3-N) in water bodies can lead to eutrophication of the aquatic environment. Therefore, it is important to develop a technology that can efficiently remove P and NH3-N from water. Here, the adsorption performance of cerium-loaded intercalated bentonite (Ce-bentonite) was optimized based on single-factor experiments using central composite design-response surface methodology (CCD-RSM) and genetic algorithm-back propagation neural network (GA-BPNN) models. Based on the determination coefficient (R2), mean absolute error (MAE), mean square error (MSE), mean absolute percentage error (MAPE), and root mean square error (RMSE), the GA-BPNN model was found to be more accurate in predicting adsorption conditions than the CCD-RSM model. The validation results showed that the removal efficiency of P and NH3-N by Ce-bentonite under optimal adsorption conditions (adsorbent dosage = 1.0 g, adsorption time = 60 min, pH = 8, initial concentration = 30 mg/L) reached 95.70% and 65.93%. Furthermore, based on the application of these optimal conditions in simultaneous removal of P and NH3-N by Ce-bentonite, pseudo-second order and Freundlich models were able to better analyze adsorption kinetics and isotherms. It is concluded that the optimization of experimental conditions by GA-BPNN has some guidance and provides a new approach to explore adsorption performance after optimizing the conditions.

Role of chemokine receptor 2 in rheumatoid arthritis: A research update.

Rheumatoid arthritis (RA) is a multisystemic and inflammatory autoimmune disease characterized by joint destruction. The C-C motif chemokine receptor 2 (CCR2) is mainly expressed in monocytes and T cells, initiating their migration to sites of inflammation, ultimately leading to cartilage damage and bone destruction. CCR2 has long been considered a prospective target for treating autoimmune diseases. However, clinical studies on inhibitors or neutralizing antibodies against CCR2 in RA have exhibited limited efficacy. Recent evidence indicates that CCR2 may play different roles in RA. Hence, a comprehensive understanding regarding the role of CCR2 may facilitate the development of targeted drugs and provide novel insights for improving CCL2-mediated inflammatory diseases. This review summarizes the biological characteristics of CCR2, the related signaling pathways, and recent developments in CCR2-targeting therapeutics.

PU.1 promotes development of rheumatoid arthritis via repressing FLT3 in macrophages and fibroblast-like synoviocytes.

OBJECTIVES: To uncover the function and underlying mechanism of an essential transcriptional factor, PU.1, in the development of rheumatoid arthritis (RA). METHODS: The expression and localisation of PU.1 and its potential target, FMS-like tyrosine kinase 3 (FLT3), in the synovium of patients with RA were determined by western blot and immunohistochemical (IHC) staining. UREΔ (with PU.1 knockdown) and FLT3-ITD (with FLT3 activation) mice were used to establish collagen antibody-induced arthritis (CAIA). For the in vitro study, the effects of PU.1 and FLT3 on primary macrophages and fibroblast-like synoviocytes (FLS) were investigated using siRNAs. Mechanistically, luciferase reporter assays, western blotting, FACS and IHC were conducted to show the direct regulation of PU.1 on the transcription of FLT3 in macrophages and FLS. Finally, a small molecular inhibitor of PU.1, DB2313, was used to further illustrate the therapeutic effects of DB2313 on arthritis using two in vivo models, CAIA and collagen-induced arthritis (CIA). RESULTS: The expression of PU.1 was induced in the synovium of patients with RA when compared with that in osteoarthritis patients and normal controls. FLT3 and p-FLT3 showed opposite expression patterns compared with PU.1 in RA. The CAIA model showed that PU.1 was an activator, whereas FLT3 was a repressor, of the development of arthritis in vivo. Moreover, results from in vitro assays were consistent with the in vivo results: PU.1 promoted hyperactivation and inflammatory status of macrophages and FLS, whereas FLT3 had the opposite effects. In addition, PU.1 inhibited the transcription of FLT3 by directly binding to its promoter region. The PU.1 inhibitor DB2313 clearly alleviated the effects on arthritis development in the CAIA and CIA models. CONCLUSIONS: These results support the role of PU.1 in RA and may have therapeutic implications by directly repressing FLT3. Therefore, targeting PU.1 might be a potential therapeutic approach for RA.

Growth arrest-specific transcript 5 represses endometrial cancer development by promoting antitumor function of tumor-associated macrophages.

The tumor-suppressor role of long noncoding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) has been proven in various types of cancer. However, the specific function of GAS5 in tumor-associated macrophages (TAMs) of endometrial cancer (EC) is elusive. Quantitative PCR results showed that GAS5 expression decreased in EC tissues and primary TAMs from EC tumors. Tumor-associated macrophage infiltration was significantly positively associated with the developmental stage of EC. Direct coculture of GAS5-overexpressing TAMs and EC cells showed that GAS5 enhanced phagocytosis, antigen presentation, and activation of cytotoxic T cells, and repressed "Don't eat me" signals between TAMs and EC cells. Tumor formation in immunodeficient mice showed that GAS5-overexpressing macrophages could repress EC formation in vivo. GAS5 promoted M1 polarization by activating the microRNA-21- phosphatase and tensin homolog (PTEN)-AKT signaling pathway and directly repressing the nuclear accumulation and phosphorylation of oncogenic yes-associated protein 1 (YAP1) in TAMs. GAS5 inhibited the development of EC from both innate and adaptive immunity by transforming TAMs from a protumor to an antitumor phenotype. These antitumor effects of GAS5 on TAMs were mediated by the activation of the miR-21-PTEN-AKT pathway and inhibition of YAP1.

MicroRNA-22 represses glioma development via activation of macrophage-mediated innate and adaptive immune responses.

Macrophage-mediated tumor cell phagocytosis and subsequent neoantigen presentation are critical for generating anti-tumor immunity. This study aimed to uncover the potential clinical value and molecular mechanisms of miRNA-22 (miR-22) in tumor cell phagocytosis via macrophages and more efficient T cell priming. We found that miR-22 expression was markedly downregulated in primary macrophages from glioma tissue samples compared to adjacent tissues. miR-22-overexpressing macrophages inhibited glioma cell proliferation and migration, respectively. miR-22 upregulation stimulated the phagocytic ability of macrophages, enhanced tumor cell phagocytosis, antigen presentation, and efficient T cell priming. Additionally, our data revealed that miR-22-overexpressing macrophages inhibited glioma formation in vivo, HDAC6 was a target, and NF-κB signaling was a pathway closely associated with miR-22 in tumor-associated macrophages (TAMs) of glioma. Our findings revealed the essential roles of miR-22 in tumor cell phagocytosis by macrophages and more efficient T cell priming, facilitating further research on phagocytic regulation to enhance the response to tumor immunotherapy.

MicroRNA-10b promotes arthritis development by disrupting CD4+ T cell subtypes.

Rheumatoid arthritis (RA) is an inflammation-involved disorder and features the disruption of CD4+ T lymphocytes. Herein, we describe that microRNA-10b-5p (miR-10b) promotes RA progression by disrupting the balance between subsets of CD4+ T cells. MiR-10b-deficient mice protected against collagen antibody-induced arthritis (CAIA) model. RNA sequencing results indicated that disordered genes in miR-10b-/- CAIA model are closely associated with CD4+ T cells differentiation. Moreover, miR-10b mimics promoted Th1/Th17 and suppressed Th2/Treg cells differentiation, whereas miR-10b inhibitor induced contrary effects. In addition, GATA3 and PTEN was confirmed as two targets of miR-10b, and GATA3 siRNA could increase Th1 and reduce Th2 cells meanwhile PTEN siRNA could increase Th17 and decrease Treg cells. Furthermore, miR-10b inhibitor significantly ameliorated collagen-induced arthritis (CIA) development by attenuating the dysfunctional CD4+ T cell subpopulations. The present findings suggest that miR-10b could disrupt the balance of CD4+ T subsets, while suppressed miR-10b could attenuate the severity of experimental arthritis, which provided us a novel mechanistic and therapeutic insight into the RA.

CAR-macrophage: A new immunotherapy candidate against solid tumors.

Chimeric antigen receptor (CAR)-T cell therapy has been shown to be an effective treatment for hematological tumors, but the treatment of solid tumors still lacks effectiveness. In the tumor microenvironment, macrophages are the innate immune cells with the highest infiltration rate. Tumor-associated macrophages (TAMs) stimulate angiogenesis, increase tumor invasion, and mediate immunosuppression. Because macrophages can infiltrate solid tumor tissue and interact with almost all cellular components in the tumor microenvironment (including tumor cells, immune cells such as T-cells, NK cells, DCs, and other resident non-immune cells), researchers are trying to use macrophages modified with CAR (CAR-M) against solid tumors. This review describes recent reports of CAR-M-based tumor treatments and summarizes their shortcomings and future applications.

The essential role of long non-coding RNA GAS5 in glioma: interaction with microRNAs, chemosensitivity and potential as a biomarker.

Glioma is a malignant brain tumor with a generally poor prognosis. Dysregulation of a long non-coding RNA, GAS5, has been detected in numerous cancers, including glioma. Previous studies have suggested that GAS5 plays a significant functional role in glioma, affecting proliferation, metastasis, invasion, and apoptosis. In this review, we describe the roles and mechanisms of GAS5 in glioma. GAS5 may be a biomarker for diagnosis and prognosis, and even a potential target for glioma treatment, and therefore warrants further investigation.

Activation of nuclear factor-κB in the angiogenesis of glioma: Insights into the associated molecular mechanisms and targeted therapies.

Glioma is the most commonly observed primary intracranial tumour and is associated with massive angiogenesis. Glioma neovascularization provides nutrients for the growth and metabolism of tumour tissues, promotes tumour cell division and proliferation, and provides conditions ideal for the infiltration and migration of tumour cells to distant places. Growing evidence suggests that there is a correlation between the activation of nuclear factor (NF)-κB and the angiogenesis of glioma. In this review article, we highlighted the functions of NF-κB in the angiogenesis of glioma, showing that NF-κB activation plays a pivotal role in the growth and progression of glioma angiogenesis and is a rational therapeutic target for antiangiogenic strategies aimed at glioma.

The emerging role of fibroblast-like synoviocytes-mediated synovitis in osteoarthritis: An update.

Osteoarthritis (OA), the most ubiquitous degenerative disease affecting the entire joint, is characterized by cartilage degradation and synovial inflammation. Although the pathogenesis of OA remains poorly understood, synovial inflammation is known to play an important role in OA development. However, studies on OA pathophysiology have focused more on cartilage degeneration and osteophytes, rather than on the inflamed and thickened synovium. Fibroblast-like synoviocytes (FLS) produce a series of pro-inflammatory regulators, such as inflammatory cytokines, nitric oxide (NO) and prostaglandin E2 (PGE2 ). These regulators are positively associated with the clinical symptoms of OA, such as inflammatory pain, joint swelling and disease development. A better understanding of the inflammatory immune response in OA-FLS could provide a novel approach to comprehensive treatment strategies for OA. Here, we have summarized recently published literatures referring to epigenetic modifications, activated signalling pathways and inflammation-associated factors that are involved in OA-FLS-mediated inflammation. In addition, the current related clinical trials and future perspectives were also summarized.

IPM strategies to a discrete switching predator-prey model induced by a mate-finding Allee effect.

This paper proposes a discrete switching predator-prey model with a mate-finding Allee effect, where also switches are guided by Allee effect. One of the strategies analysed is to use a chemical in order to prevent the pest outbreak when the pest population is free of Allee effect. In this paper, we first study analytically the dynamic behaviors of the two subsystems and the equilibria and their stability of the switched system. Then we provide numerical bifurcation analyses for the switched discrete system. These show that the switched discrete system may have very complex dynamics by 2-parameter bifurcation diagrams which divide the space into regions and study equilibria, and 1-dimensional bifurcation diagrams which reveal that the system has periodic, chaotic solutions, period doubling bifurcations and so on. Furthermore, we try to refer the key parameters and initial densities of both populations associated with pest outbreaks and study their biological implications.