Objective To investigate the effects of monocyte chemotactic protein-4(MCP-4)on pyroptosis and p38 mitogen-activated protein kinase(p38 MAPK)activation in human nasal epithelial cells(HNEpCs).Methods Forty patients diagnosed with chronic rhinosinusitis(CRS)were selected as the case group,and another 40 healthy individuals were selected as the normal group.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of MCP-4 in serum samples from both groups.Receiver operator characteristic(ROC)curve analysis was performed to assess the diagnostic efficacy of serum MCP-4 levels for CRS.HNEpCs were divided into six groups:control group,5 mg/L lipopolysaccharide(LPS)model group,LPS+siRNA negative control(si-Con)group,LPS+siRNA MCP-4(si-MCP-4)group,LPS+pcDNA3.1-vector group,and LPS+pcDNA3.1-MCP-4 group.Cell viability was assessed using the cell counting kit-8(CCK-8),and cell proliferation activity was detected by 5-Ethynyl-2'-deoxyuridine(EdU)staining.Western blot was used to detect the expression levels of phosphorylated p38 MAPK(p-p38 MAPK),Gasdermin D(GSDMD),NOD-like receptor family,pyrin domain containing 3(NLRP3),apoptosis-associated speck-like protein(ASC),and caspase-1.ELISA was performed to measure the levels of tumor necrosis factor-α(TNF-α),interleukin-18(IL-18),and IL-1β in cell supernatants.The Transwell chamber was utilized to assess the effects of MCP-4 on the migratory capacity of HNEpCs.HNEpCs were divided into four groups:control group,10 ng/ml MCP-4 group,and 20 ng/ml MCP-4 group.Results Compared with the normal group,the level of MCP-4 in the serum of patients in the case group was significantly upregulated.ROC curve analysis showed that the area under the curve(AUC)for serum MCP-4 levels in the diagnosis of CRS was 0.921.In vitro experiments demonstrated that LPS stimulation reduced the survival rate and proliferation ability of HNEpCs,increased the expression of pyroptosis proteins,and upregulated p-p38 MAPK levels,and increased the release of TNF-α,IL-1β,and IL-18(P<0.01).Compared with the LPS model group,the LPS+si-MCP-4 group showed increased survival rate and proliferation ability of HNEpCs,decreased expression levels of p-p38 MAPK,pyroptosis proteins and reduced levels of TNF-α,IL-1β,and IL-18(P<0.01).In contrast,compared with the LPS model group,the LPS+pcDNA3.1-MCP-4 group exhibited further decreased survival rate and proliferation ability of HNEpCs,increased expression levels of p-p38 MAPK,pyroptosis proteins,and elevated levels of inflammatory cytokines TNF-α,IL-1β,and IL-18(P<0.01).Compared with the control group,there was no significant increase in the migration ability of HNEpCs in the 10 ng/mL MCP-4 and 20 ng/ml MCP-4 groups.Conclusion Inhibiting the expression of MCP-4 can block the activation of p38 MAPK,reducing pyroptosis and the release of inflammatory cytokines in HNEpCs.

Atherosclerosis(AS)is a chronic inflammatory disease of large and medium-sized arteries that leads to ischemic heart disease,stroke,and peripheral vascular disease.Despite the current treatments,mortality and disability still remain high.Sonodynamic therapy(SDT),a non-invasive and localized methodology,has been developed as a promising new treatment for inhibiting atherosclerotic progression and sta-bilizing plaques.Promising progress has been made through cell and animal assays,as well as clinical trials.For example,the effect of SDT on apoptosis and autophagy of cells in AS,especially macrophages,and the concept of non-lethal SDT has also been proposed.In this review,we summarize the ultrasonic parameters and known sonosensitizers utilized in SDT for AS;we elaborate on SDTs therapeutic effects and mechanisms in terms of macrophages,T lymphocytes,neovascularization,smooth muscle cells,lipid,extracellular matrix and efferocytosis within plaques;additionally,we discuss the safety of SDT.A comprehensive summary of the confirmed effects of SDT on AS is conducted to establish a framework for future researchers.

Objective To investigate the effects of monocyte chemotactic protein-4(MCP-4)on pyroptosis and p38 mitogen-activated protein kinase(p38 MAPK)activation in human nasal epithelial cells(HNEpCs).Methods Forty patients diagnosed with chronic rhinosinusitis(CRS)were selected as the case group,and another 40 healthy individuals were selected as the normal group.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of MCP-4 in serum samples from both groups.Receiver operator characteristic(ROC)curve analysis was performed to assess the diagnostic efficacy of serum MCP-4 levels for CRS.HNEpCs were divided into six groups:control group,5 mg/L lipopolysaccharide(LPS)model group,LPS+siRNA negative control(si-Con)group,LPS+siRNA MCP-4(si-MCP-4)group,LPS+pcDNA3.1-vector group,and LPS+pcDNA3.1-MCP-4 group.Cell viability was assessed using the cell counting kit-8(CCK-8),and cell proliferation activity was detected by 5-Ethynyl-2'-deoxyuridine(EdU)staining.Western blot was used to detect the expression levels of phosphorylated p38 MAPK(p-p38 MAPK),Gasdermin D(GSDMD),NOD-like receptor family,pyrin domain containing 3(NLRP3),apoptosis-associated speck-like protein(ASC),and caspase-1.ELISA was performed to measure the levels of tumor necrosis factor-α(TNF-α),interleukin-18(IL-18),and IL-1β in cell supernatants.The Transwell chamber was utilized to assess the effects of MCP-4 on the migratory capacity of HNEpCs.HNEpCs were divided into four groups:control group,10 ng/ml MCP-4 group,and 20 ng/ml MCP-4 group.Results Compared with the normal group,the level of MCP-4 in the serum of patients in the case group was significantly upregulated.ROC curve analysis showed that the area under the curve(AUC)for serum MCP-4 levels in the diagnosis of CRS was 0.921.In vitro experiments demonstrated that LPS stimulation reduced the survival rate and proliferation ability of HNEpCs,increased the expression of pyroptosis proteins,and upregulated p-p38 MAPK levels,and increased the release of TNF-α,IL-1β,and IL-18(P<0.01).Compared with the LPS model group,the LPS+si-MCP-4 group showed increased survival rate and proliferation ability of HNEpCs,decreased expression levels of p-p38 MAPK,pyroptosis proteins and reduced levels of TNF-α,IL-1β,and IL-18(P<0.01).In contrast,compared with the LPS model group,the LPS+pcDNA3.1-MCP-4 group exhibited further decreased survival rate and proliferation ability of HNEpCs,increased expression levels of p-p38 MAPK,pyroptosis proteins,and elevated levels of inflammatory cytokines TNF-α,IL-1β,and IL-18(P<0.01).Compared with the control group,there was no significant increase in the migration ability of HNEpCs in the 10 ng/mL MCP-4 and 20 ng/ml MCP-4 groups.Conclusion Inhibiting the expression of MCP-4 can block the activation of p38 MAPK,reducing pyroptosis and the release of inflammatory cytokines in HNEpCs.

The prevalence of obesity-associated conditions raises new challenges in clinical medication. Although altered expression of drug-metabolizing enzymes (DMEs) has been shown in obesity, the impacts of obese levels (overweight, obesity, and severe obesity) on the expression of DMEs have not been elucidated. Especially, limited information is available on whether parental obese levels affect ontogenic expression of DMEs in children. Here, a high-fat diet (HFD) and three feeding durations were used to mimic different obese levels in C57BL/6 mice. The hepatic expression of five nuclear receptors (NRs) and nine DMEs was examined. In general, a trend of induced expression of NRs and DMEs (except for and ) was observed in HFD groups compared to low-fat diet (LFD) groups. Differential effects of HFD on the hepatic expression of DMEs were found in adult mice at different obese levels. Family-based dietary style of an HFD altered the ontogenic expression of DMEs in the offspring older than 15 days. Furthermore, obese levels of parental mice affected the hepatic expression of DMEs in offspring. Overall, the results indicate that obese levels affected expression of the DMEs in adult individuals and that of their children. Drug dosage might need to be optimized based on the obese levels.

Objective To explore the effects and mechanism of repetitive transcranial magnetic stimulation (rTMS) applied to the right Broca's homologue of stroke patients with non-fluent aphasia.Methods One stroke patient with non-fluent aphasia received rTMS at 1 Hz and another received the same treatment at 10 Hz.The western aphasia battery (WAB) and functional magnetic resonance imaging (fMRI) were used to evaluate their language function before and after the intervention.Results After treatment,language function in both patients had improved significantly.The aphasia quotient (AQ) score of patient 1 had improved from 37.2 to 66.6,and the AQ score of patient 2 had improved from 36.2 to 60.8.Before treatment,patient 1's activated brain areas during a vocabulary reading task were the left anterior central gyrus and the left gyrus frontalis medius.After the 1 Hz rTMS treatment the activated brain areas were the left medial surface of the lobus frontalis,the left gyrus frontalis inferior,the left prefrontal area,the left preinsula,the left lobulus parietalis inferior,and the left middle/inferior temporal gyrus.Before the 10 Hz rTMS treatment,patient 2's activated brain areas with the same vocabulary reading task were the bilateral medial surface of the temporal lobe,and the bilateral anterior central gyrus.After treatment the bilateral medial surface gyrus,the frontalis medius and lobus frontalis,the right gyrus frontalis inferior,the left prefrontal area,the bilateral lobulus parietalis superior,and the right superior/middle temporal gyrus were activated.Conclusion rTMS can significantly improve language function in stroke patients with non-fluent aphasia.Patients with smaller lesions in the left hemisphere language area can achieve hemisphere function restructuring.Larger lesions in the left hemisphere language area will probably yield bilateral restructuring in both hemispheres.