Volatile oil of Angelica sinensis Radix improves cognitive function by inhibiting miR-301a-3p targeting Ppp2ca in cerebral ischemia mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Angelica Sinensis Radix (ASR) is a commonly used Chinese medicine known for its effects on tonifying blood, promoting blood circulation, and alleviating pain associated with menstrual regulation. Additionally, it has been used in the treatment of vascular cognitive impairment (VCI). The primary pharmacodynamic agent within ASR is volatile oil of Angelica Sinensis Radix (VOASR), which has demonstrated efficacy in combating cognitive impairment, although its mechanism remains unclear. OBJECTIVE: This study aimed to elucidate the potential molecular mechanisms underlying VOASR's improvement of cognitive function in cerebral ischemic mice. METHODS: A model of cerebral ischemic mice was established through unilateral common carotid artery occlusion (UCCAO) surgery, followed by intervention with VOASR. Cognitive function was assessed using the Morris water maze (MWM) test, while RT-qPCR was utilized to measure the differential expression of miR-301a-3p in the hippocampus. To evaluate cognitive function and hippocampal protein differences, wild-type mice and miR-301a-3p knockout mice were subjected to the MWM test and iTRAQ protein profiling. The relationship between miR-301a-3p and potential target genes was validated through a Dual-Luciferase Reporter experiment. RT-qPCR and Western blot were employed to determine the differential expression of Ppp2ca and synaptic plasticity-related proteins in the mouse hippocampus. RESULTS: Intervention with VOASR significantly improved cognitive impairment in cerebral ischemic mice and reduced the expression of miR-301a-3p in the hippocampus. Our findings suggest that miR-301a-3p may regulate cognitive function by targeting Ppp2ca. Furthermore, VOASR intervention led to an increase in the expression of Ppp2ca and synaptic plasticity-related proteins. CONCLUSION: Our study indicates that VOASR may be involved in regulating cognitive function by inhibiting miR-301a-3p, consequently increasing the expression of Ppp2ca and synaptic plasticity proteins. These results provide a new target and direction for the treatment of cognitive dysfunction.

Characteristics of ambient air quality and its air quality index (AQI) model in Shanghai, China.

Long-term observations indicate that, the ambient air quality in Shanghai continues to improve, however the synergistic effects between the air pollutants PM2.5, O3 and NO2 are also increasing. The concentration of chemical components included in PM2.5 is higher in moderately polluted air containing multiple pollutants. This suggests that air pollution metrics based on multi-pollutant synergy are more descriptive of ambient air quality than single-pollutant air quality index (AQI) models that may ignore the effect of synergy between pollutants on ambient air quality forecasts. Therefore, this study proposes a new multi-pollutant air quality index model (NMAQI) based on four air pollutants (PM2.5, SO2, NO2 and O3) that emphasizes the relationship between PM2.5, NO2 and O3 in ambient air. The model successfully categorized observational data into classes of good, moderate, and polluted air quality ratings. Verification of the NMAQI model using the PM2.5 chemical composition spectrum shows that the NMAQI model can more accurately classify samples with high concentrations of chemical components (often misclassified by AQI) into high pollution levels. The model has an improved capacity to assess the degree of pollution in urban ambient air and to reduce the risk of public exposure to highly polluted atmospheric environments.

IL16 Regulates Osteoarthritis Progression as a Target Gene of Novel-miR-81.

OBJECTIVE: Functional polymorphisms of interleukin 16 (IL16) have been reported to be closely related to the risk of osteoarthritis (OA). However, how IL16 affects OA remains unclear. In this study, the role of IL16 in OA and the possible mechanisms were examined. METHODS: We established a meniscal/ligament injury (MLI) post-traumatic OA model in Sprague Dawley rats and an IL1ß-induced ADTC5 cells OA model. We detected the expression of IL16, novel-miR-81, MMP3, and MMP13 by quantitative real-time polymerase chain reaction. Western blot was performed to detect the expression of IL16, MMP3, and MMP13. The association between IL16 and novel-miR-81 was confirmed by luciferase reporter assay. Hematoxylin and eosin staining, Safranin O and Fast Green staining, and immunohistochemical staining were performed to clarify the effect of intra-articular injection of novel-miR-81 agomir in rats OA model. RESULTS: IL16 was upregulated in OA model. Knockdown of IL16 and overexpression of novel-miR-81 downregulated the expression of MMP3 and MMP13. Importantly, IL16 was a key target of novel-miR-81. Intra-articular injection of novel-miR-81 agomir could attenuate OA progression in rats OA model. CONCLUSION: Novel-miR-81 targeted IL16 to relieve OA, suggesting that novel-miR-81and IL16 may be new therapeutic targets for OA.

Satisfactory Wound Reconstruction with a Local Rotation Flap After Removal of Large Penile Divided Nevi: Original Technique, Early and Mid-Term Results.

Objective: To investigate the application of local rotation flaps for reconstruction of divided nevi of the penises in young male patients. Methods: A group of 8 patients of divided nevi of the penises who underwent wound reconstruction with local rotation flaps after surgical lesion removal was enrolled in a retrospective clinical study. Postoperative complication, sexual function and psychological traits were evaluated during the follow-up. Results: All patients, with ages ranged from 16 to 32 years (mean 23.25 years), were followed up for 6 to 48 months (mean 19.86 months). The patient's average length of hospital stay was 7.85 day (7 to 15 days). The average dimension of the lesions was (2.31±0.44) × (1.46±0.48) cm2 on the glans and (1.38±0.40) × (1.01±0.46) cm2 on the inner prepuce plate. All patients had no postoperative infection and were satisfied with the postoperative outcome upon discharge. Five cases of benign intradermal nevi and 3 cases of compound nevi without malignant transformation were confirmed by pathological evaluation on the removed samples. The sexual function of all patients was unaffected postoperatively by male sexual function scale (BMSFI and IIEF-5) evaluation. The psychological status of depression, anxiety and stress was all improved after the surgical reconstruction confirmed by the psychological traits scale (DASS) evaluation. Conclusion: Reconstruction with the local rotation flap is a simple, safe and appropriate surgical procedure, achieves satisfactory cosmetic outcome, and maintains intact male sexual function when used for the repair of defect after removal of divided nevi of the penises.

Burden of tuberculosis and its association with socio-economic development status in 204 countries and territories, 1990-2019.

Background: Tuberculosis (TB) always runs in the forefront of the global burden when it comes to infectious diseases. Tuberculosis, which can lead to impairment of quality of life, financial hardship, discrimination, marginalization, and social barriers, is a major public health problem. The assessment of TB burden and trend can provide crucial information for policy decision and planning, and help countries in the world to achieve the goal of sustainable development of ending the epidemic of TB in 2030. Methods: All data are from the Global Burden of Disease 2019 (GBD 2019) database, which analyzed the burden trend of age-standardized incidence, DALYs, and deaths rate in TB and HIV/AIDS-infected TB over the past 30 years. Also, GBD 2019 not only analyzed the burden distribution of TB in 204 countries and main regions of the world but also analyzed the relationship between the burden of global TB and the socio-demographic Index (SDI). Results: The age-standardized incidence, age-standardized disability-adjusted life years (DALYs), and age-standardized deaths rate for HIV-negative TB were 10,671.45 (9,395.60-12,194.10), 59,042.45 (53,684.78-64,641.53), and 1,463.62 (1,339.24-1,602.71) (95% CI, per 100,000 person-years) in 2019, respectively. Age-standardized incidence, age-standardized DALYs, and age-standardized deaths rate of HIV/AIDS-XDR-TB (95% CI, per 1,000 person-years) were 2.10 (1.51-2.90), 64.23 (28.64-117.74), and 1.01 (0.42-1.86), respectively. We found that TB is inversely proportional to SDI, the age-standardized incidence, DALYs, and deaths rate low burden countries were in high SDI areas, while high burden countries were in low SDI areas. The global TB showed a slow decline trend, but the age-standardized incidence of HIV-positive TB was increasing, and mainly distributed in sub-Saharan Africa. Conclusion: Age-standardized incidence, age-standardized DALYs, and age-standardized deaths rate of TB is related to SDI, and the burden of low SDI countries is lighter than that of high SDI countries. Without effective measures, it will be difficult for countries around the world to achieve the goal of ending the TB epidemic by 2030. Effective control of the spread of TB requires concerted efforts from all countries in the world, especially in the countries with low SDI, which need to improve the diagnosis and preventive measures of TB and improve the control of HIV/AIDS-TB.

Identification of Important Modules and Biomarkers That Are Related to Immune Infiltration Cells in Severe Burns Based on Weighted Gene Co-Expression Network Analysis.

Background: Immunosuppression is an important trigger for infection and a significant cause of death in patients with severe burns. Nevertheless, the prognostic value of immune-related genes remains unclear. This study aimed to identify the biomarkers related to immunosuppression in severe burns. Methods: The gene expression profile and clinical data of 185 burn and 75 healthy samples were obtained from the GEO database. Immune infiltration analysis and gene set variation analysis were utilized to identify the disorder of circulating immune cells. A weighted gene co-expression network analysis (WGCNA) was carried out to select immune-related gene modules. Enrichment analysis and protein-protein interaction (PPI) network were performed to select hub genes. Next, LASSO and logistic regression were utilized to construct the hazard regression model with a survival state. Finally, we investigated the correlation between high- and low-risk patients in total burn surface area (TBSA), age, and inhalation injury. Results: Gene set variation analysis (GSVA) and immune infiltration analysis showed that neutrophils increased and T cells decreased in severe burns. In WGCNA, four modular differently expressed in burns and controls were related to immune cells. Based on PPI and enrichment analysis, 210 immune-related genes were identified, mainly involved in T-cell inhibition and neutrophil activation. In LASSO and logistic regression, we screened out key genes, including LCK, SKAP1 and GZMB, and LY9. In the ROC analysis, the area under the curve (AUC) of key genes was 0.945, indicating that the key genes had excellent diagnostic value. Finally, we discovered that the key genes were related to T cells, and the regression model performed well when accompanied by TBSA and age. Conclusion: We identified LCK, SKAP1, GZMB, and LY9 as good prognostic biomarkers that may play a role in post-burn immunosuppression against T-cell dysfunction and as potential immunotherapeutic targets for transformed T-cell dysfunction.

Foamy macrophages potentially inhibit tuberculous wound healing by inhibiting the TLRs/NF-κB signalling pathway.

To characterise the distribution, classification, and quantity of foamy macrophages (FMs) in tuberculous wound tissue and the relationship between FM and delayed healing of tuberculous wounds. Morphological studies were performed to explore the distribution of FM and Mycobacterium tuberculosis (Mtb) in tuberculous wounds, with acute and chronic wounds included for comparison. Phorbol-12-myristate-13-acetate stimulation-differentiated THP-1 cells were treated with Mtb to induce their differentiation into FM with oxidised low-density lipoprotein treatment serving as a control. Relative cytokine levels were determined by quantitative PCR and Western blotting. Varied co-culture combinations of Mtb, THP-1, FM, and fibroblasts were performed, and proliferation, migration, ability to contract collagen gel, and protein levels of the chemokines in the supernatants of the fibroblasts were assessed. The differentially expressed genes in human skin fibroblasts (HSFs) after co-culture with or without FM were identified using microarray. Many FM were found in the tissues of tuberculous wounds. The FM that did not engulf Mtb (NM-FM) were mainly distributed in tissues surrounding tuberculous wounds, whereas the FM that engulfed Mtb (M-FM) were dominantly located within granulomatous tissues. Co-culture experiments showed that, with the Mtb co-culture, the portions of NM-FM in the total FM grew over time. The migration, proliferation, chemokine secretion, and the ability of fibroblasts to contract collagen gel were inhibited when co-cultured with Mtb, FM, or a combination of the two. Further investigation showed that the TLRs/NF-κB signalling pathway is involved in fibroblast function under the stimulation of FM. TLRs and NF-κB agonists could reverse the phenotypic changes in HSFs after co-culture with FM. The tuberculous wound microenvironment composed of Mtb and FM may affect wound healing by inhibiting the functions of fibroblasts. FM potentially inhibit fibroblasts' function by inhibiting the TLRs/NF-κB signalling pathway in tuberculous wounds.

Effects of the long and short isoforms of TIPE3 on the growth and metastasis of gastric cancer.

Tumor necrosis factor alpha-induced protein 8-like 3 (TIPE3, also known as TNFAIP8L3) plays a vital role in tumorigenesis and development. However, it is unclear whether the two transcript variants of TIPE3 (long TIPE3 and short TIPE3) have an effect on the proliferation and metastasis of gastric cancer (GC). In this study, we demonstrated that the expression of TIPE3 decreased in GC, but patient prognosis worsened as TIPE3 expression increased. Then, overexpression models were constructed to study the role of long TIPE3 and short TIPE3. Upregulation of long TIPE3 and short TIPE3 promoted GC cell proliferation and metastasis both in vitro and in vivo, and the effect of short TIPE3 was more obvious. Further studies demonstrated that long TIPE3 and short TIPE3 promoted proliferation and metastasis of GC cells vis PI3K/Akt pathway. In conclusion, the two TIPE3 isoforms play an important role in the tumorigenesis of GC and depend on the activation of the PI3K/Akt pathway.

Effects of A94T and P84L Polymorphisms Within the TNF-α Gene on Proliferation and Activation of Hepatic Stellate Cells.

Tumor necrosis factor alpha (TNF-α) appears to play an important role in proliferation and activation of hepatic stellate cells (HSCs), but it is unclear whether single nucleotide polymorphisms (SNPs) in the TNF-α gene influence HSCs function. In this study, we explored the effects of TNF-α A94T and P84L polymorphisms on the level of TNF-α, proliferation and activation of HSCs. It was found that A94T and P84L SNPs of TNF-α downregulated the mRNA and protein level of TNF-α in recombinant cells. Compared with wild-type TNF-α, A94T and P84L SNPs could decrease the growth or activation inhibitory effects of TNF-α on LX-2 cells, the human HSC line. In addition, A94T SNPs were associated with significantly lower expression of matrix-metalloproteinase 2 (MMP 2) or 9, but P84L SNP only decreased the mRNA level of MMP 9. A94T and P84L SNPs of TNF-α downregulated the level of IL-6. Furthermore, A94T and P84L SNPs decrease the activation inhibitory effects of TNF-α on LX-2 cells through inhibiting the phosphorylation levels of inhibitory kappa B-alpha (IκB-α) and P65. This study provides two vital SNPs for further functional or case-control studies of TNF-α SNPs.

Associations of the IL-17A rs2275913 and IL-17F rs763780 polymorphisms with the risk of digestive system neoplasms: A meta-analysis.

OBJECTIVE: To clarify the associations between the IL-17A rs2275913 and IL-17F rs763780 polymorphisms and the risk of digestive system neoplasms. METHODS: An internet search was used to identify relevant articles from CNKI, Wanfang, VIP, PubMed, EMBASE and Elsevier up to December 2017. The meta-analysis was performed using Stata 11.0 software. RESULTS: Twenty-three studies were included. Among these, 21 studies with 6978 cases and 8000 controls were related to IL-17A rs2275913, while 18 studies that included 5073 cases and 6040 controls were related to IL-17F rs763780. The meta-analysis results demonstrated that the overall effects of the two polymorphisms were significantly different (P < 0.05) in the allele model, dominant model, recessive model and codominant model. Subgroup analysis showed that both polymorphisms were significantly associated with susceptibility to gastric cancer but not with hepatocellular carcinoma or colorectal cancer. In the ethnicity analysis, these two polymorphisms were associated with Asian populations but not with Caucasians. Similar results were observed in the hospital-based and population-based control subgroups. CONCLUSIONS: The IL-17A rs2275913 and IL-17F rs763780 polymorphisms were associated with susceptibility to digestive system neoplasms.