Perspectives on the Trypanosoma cruzi-host cell receptor interaction

Chagas disease is caused by the parasite Trypanosoma cruzi. The critical initial event is the interaction of the trypomastigote form of the parasite with host receptors. This review highlights recent observations concerning these interactions. Some of the key receptors considered are those for thromboxane, bradykinin, and for the nerve growth factor TrKA. Other important receptors such as galectin-3, thrombospondin, and laminin are also discussed. Investigation into the molecular biology and cell biology of host receptors for T. cruzi may provide novel therapeutic targets

Dietary Walnuts Protect Against Obesity-Driven Intestinal Stem Cell Decline and Tumorigenesis

Obesity can negatively impact intestinal homeostasis, and increase colon cancer risk and related mortality. Thus, given the alarmingly high rates of obesity in the US and globally, it is critical to identify practical strategies that can break the obesity-cancer link. Walnuts have been increasingly recognized to mitigate cancer risk, and contain many bioactive constituents with antioxidant and anti-inflammatory properties that could potentially counteract pathways thought to be initiators of obesity-related cancer. Therefore, the purpose of this study was to determine if walnuts could preserve intestinal homeostasis, and attenuate tumorigenesis and growth in the context of obesity and a high calorie diet. To this end, we studied effects of walnuts on these parameters under different dietary conditions in wildtype mice, two independent Apc models (Apc1638N/+ and ApcΔ14), and in MC38 colon cancer cells in vivo, respectively. Walnuts did not alter the metabolic phenotype or intestinal morphology in normal mice fed either a low-fat diet (LFD), LFD with 6% walnuts (LFD+W), high-fat diet (HFD), or HFD with 7.6% walnuts (HFD+W). However, walnuts did lead to a significant reduction in circulating CCL5 and preserved intestinal stem cell (ISC) function under HFD-fed conditions. Furthermore, walnuts reduced tumor multiplicity in Apc1638N/+ male HFD+W animals, as compared to HFD controls (3.7 ± 0.5 vs. 2.5 ± 0.3; P = 0.015), tended to reduce the number of adenocarcinomas (0.67 ± 0.16 vs. 0.29 ± 0.12; P = 0.07), and preferentially limited tumor growth in ApcΔ14 male mice (P = 0.019) fed a high-calorie western-style diet. In summary, these data demonstrate that walnuts confer significant protection against intestinal tumorigenesis and growth and preserve ISC function in the context of a high-calorie diet and obesity. Thus, these data add to the accumulating evidence connecting walnuts as a potentially effective dietary strategy to break the obesity-colon cancer link

Construction and validation of a novel prognostic signature for cutaneous melanoma based on ferroptosis-related genes

Ferroptosis, a recently uncovered iron-dependent, non-apoptotic cell death process, has been increasingly linked to cancer development. In this study, our objective was to develop a prognostic model centered on ferroptosis-related genes (FRGs) and assess its efficacy as an overall survival (OS) prediction biomarker. We conducted a systematic analysis of cutaneous melanoma (CM) and devised a novel ferroptosis-related prognostic signature (FRGSig) using the TCGA database. An independent dataset from GSE65904 was employed to corroborate the validity of the FRGSig. Both univariate and multivariate Cox proportional hazard regression analyses were utilized to construct a FRGSig composed of five FRGs. mRNA expression and immunohistochemistry (IHC) analysis demonstrated that the expression of FRGSig genes varied between tumor and normal tissues. According to Kaplan-Meier analysis, patients with elevated FRGsig scores faced a worse prognosis. The predictive accuracy of FRGSig was evaluated using the time-dependent receiver operating characteristic curve (ROC), with the area under the curve (AUC) values for 1, 3, and 5 OS at 0.682, 0.711, 0.735 in the TCGA cohort, and 0.662, 0.695, 0.712 in the validation dataset, respectively. Univariate and multivariate Cox regression analyses demonstrated that FRGSig served as an independent prognostic factor. Further analysis revealed a significant relationship between FRGSig and Tumor Mutational Burden (TMB) as well as immune infiltration levels. Gene set enrichment analysis (GSEA) disclosed functional disparities between high- and low-risk groups, suggesting that immune checkpoint-related pathways could be instrumental in the improved prognosis of the low-risk group. Taken together, the FRGSig has potential guidance for prognosis prediction and clinical treatment of CM

Applications and Mechanisms of Stimuli-Responsive Hydrogels in Traumatic Brain Injury

Traumatic brain injury (TBI) is a global neurotrauma with high morbidity and mortality that seriously threatens the life quality of patients and causes heavy burdens to families, healthcare institutions, and society. Neuroinflammation and oxidative stress can further aggravate neuronal cell death, hinder functional recovery, and lead to secondary brain injury. In addition, the blood–brain barrier prevents drugs from entering the brain tissue, which is not conducive to the recovery of TBI. Due to their high water content, biodegradability, and similarity to the natural extracellular matrix (ECM), hydrogels are widely used for the delivery and release of various therapeutic agents (drugs, natural extracts, and cells, etc.) that exhibit beneficial therapeutic efficacy in tissue repair, such as TBI. Stimuli-responsive hydrogels can undergo reversible or irreversible changes in properties, structures, and functions in response to internal/external stimuli or physiological/pathological environmental stimuli, and further improve the therapeutic effects on diseases. In this paper, we reviewed the common types of stimuli-responsive hydrogels and their applications in TBI, and further analyzed the therapeutic effects of hydrogels in TBI, such as pro-neurogenesis, anti-inflammatory, anti-apoptosis, anti-oxidation, and pro-angiogenesis. Our study may provide strategies for the treatment of TBI by using stimuli-responsive hydrogels

Human umbilical cord blood-derived mesenchymal stem cells inhibit C6 glioma via downregulation of cyclin D1

Aims and Background: Glioma is difficult to treat and despite advances, outcomes remain poor and new treatment modalities are required. We studied the inhibitive effects of human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) on glioma growth. Material and Methods: UCB-MSCs were identified in mice by flow cytometric analysis, and neurogenic differentiation by immunohistochemistry. C6 cells were injected subcutaneously into the posterior right flank of each mouse. Dil-labeled UCB-MSCs were administrated by intravenous (IV) or intratumoral (IT) injection. Tumor blood vessel density was detected by counting the number of CD34-positive cells with endothelial morphology. Cyclin D1 protein expression was detected by immunohistochemistry and Western blot analysis. Results: A 26% reduction in overall tumor volume was observed after IV UCB-MSCs treatment, 36% in animals who received IT UCB-MSCs. UCB-MSC administration was associated with reduced neovascularization. We identified a 48% and 27% reduction in the number of cyclin D1-positive cells in mouse glioma tissues treated with UCB-MSCs IV and IT, respectively. Conclusion: We demonstrated that UCB-MSCs potently inhibit glioma growth, reduce neovascularization, and decrease cyclin D1 protein expression in vivo. IV or IT UCB-MSC administration significantly inhibits glioma growth, and may represent a promising new therapy

Surface Modification of Esophageal Stent Materials by a Drug-Eluting Layer for Better Anti-Restenosis Function

It is generally accepted that stent implantation is the mainstream therapy in clinics for esophageal cancer in the later period. However, the restenosis caused by tumor cells, epithelial cells, and fibroblasts seriously interferes with the stent medical application and limits its long-term services. To address this conundrum, a series of drug-eluting stents were invented and verified to be feasible in the early stage after implantation, but the limited drug loading and good cell compatibility of the stent materials may lead to more serious restenosis and further endanger the patient’s life. In previous work, we modified the esophageal stent material 317L stainless steel (317L SS) surface with a poly-dopamine/poly-ethylenimine layer (PDA/PEI), which had strong anti-tumor functions. In this contribution, we employed a usual drug in clinic, 5-fluorouracil (5-Fu), with series of density onto the PDA/PEI modified 317L SS to investigate the influence of 5-Fu immobilization on the anti-restenosis function. The surface characterization including 5-Fu quantity, atomic force microscopy (AFM). Water contact angle measurement indicated successful preparation of the PDA/PEI/5-Fu layers. The spectrophotometric characterization revealed that the immobilized 5-Fu rapidly released over 24 h. However, the Eca109, Het-1A, and L929 cells culture results suggested that the released 5-Fu made a significant contribution to improving the apoptosis and necrosis of these pathological cells, and the PDA/PEI/5-Fu layers maintain the consistent anti-restenosis function on their surfaces with the PDA/PEI layer after 24 h. All the results demonstrated the PDA/PEI/5-Fu layers’ excellent ability to suppress esophageal tumor cells, epithelial cells, and fibroblasts, suggesting a potential application on the surface modification of esophageal stents for better anti-restenosis function

Correction: Ren et al. Injectable and Antioxidative HT/QGA Hydrogel for Potential Application in Wound Healing. <i>Gels</i> 2021, <i>7</i>, 204

In the original publication [...

Injectable and Antioxidative HT/QGA Hydrogel for Potential Application in Wound Healing

Hydrogels have gained a niche in the market as wound dressings due to their high water content and plasticity. However, traditional hydrogel wound dressings are difficult to fully adapt to irregular-shaped wound areas. Additionally, excessive reactive oxygen species (ROS) accumulated in the damaged area impede the wound healing process. Therefore, hydrogels with injectable and antioxidant properties offer promising qualities for wound healing, but their design and development remain challenges. In this study, HT/QGA (tyramine-grafted hyaluronic acid/gallic acid-grafted quaternized chitosan) hydrogels with injectable and antioxidant properties were prepared and characterized. This hydrogel exhibited excellent injectability, favorable antioxidant activity, and good biocompatibility. Moreover, we evaluated the therapeutic effect of HT/QGA hydrogel in a full-thickness skin injury model. These results suggested that HT/QGA hydrogel may offer a great potential application in wound healing