Biological Activities of p-Hydroxycinnamic Acids in Maintaining Gut Barrier Integrity and Function.

It is well established that p-Hydroxycinnamic acids (HCAs), including ferulic, caffeic, sinapic, and p-coumaric acids, possess a characteristic phenylpropanoid C6-C3 backbone and account for about one-third of the phenolic compounds in our diet. HCAs are typically associated with various plant cell wall components, including mono-, di-, and polysaccharides, sterols, polyamines, glycoproteins, and lignins. Interestingly, enzymes produced by intestinal microbes liberate HCAs from these associations. HCAs are completely absorbed in their free form upon ingestion and undergo specific reactions upon absorption in the small intestine or liver. The gut epithelium, composed of intestinal epithelial cells (IECs), acts as a physical barrier against harmful bacteria and a site for regulated interactions between bacteria and the gut lumen. Thus, maintaining the integrity of the epithelial barrier is essential for establishing a physiochemical environment conducive to homeostasis. This review summarizes the protective effects of HCAs on the intestinal barrier, achieved through four mechanisms: preserving tight junction proteins (TJPs), modulating pro-inflammatory cytokines, exerting antioxidant activity, and regulating the intestinal microbiota.

Effect of cone-beam computed tomography image-guidance on the setup errors of stereotactic body radiotherapy for spinal metastatic tumors / 肿瘤研究与临床

Objective:To evaluate the effect of image-guided with cone-beam computed tomography (CBCT) based on volumetric modulated arc therapy (VMAT)-flattening filter free (FFF) on the setup errors of stereotactic body radiotherapy (SBRT) in patients with spinal metastatic tumors.Methods:The clinical data of 15 patients with spinal metastatic tumors who underwent SBRT in Jilin Cancer Hospital from August 2020 to January 2022 were retrospectively analyzed. The radiotherapy dose of bone metastasis was 32 Gy per 4 times and CBCT scanning was performed before and after radiotherapy. Every patient received radiotherapy 4 times; all 15 patients underwent SBRT 60 times in total and 120 CBCT volume images were finally obtained and analyzed. The systematic error (Σ) and random error (σ) were calculated at different correction threshold levels. The translational setup error and rotational setup error at the left-right (X axis), head-foot (Y axis) and front-back (Z axis) directions before and after radiotherapy were compared, which were expressed as Σ ± σ.Results:The pre-SBRT and post-SBRT translational setup errors were (0.14±0.27) cm and (0.07±0.19) cm, respectively ( P<0.001) in the X direction, (-0.05±0.33) cm and (0.00±0.19) cm, respectively ( P = 0.001) in the Y direction, (-0.13±0.19) cm and (-0.02±0.14) cm, respectively ( P = 0.012) in the Z direction. The pre-SBRT and post-SBRT rotational setup errors were (-0.31±0.76)° and (-0.09±0.34)°, respectively ( P < 0.001) in the X direction, (-0.13±0.88)° and (-0.07±0.36) °, respectively ( P < 0.001) in the Y direction, (0.10±0.51)° and (0.16±0.38)°, respectively ( P < 0.001) in the Z direction. Conclusions:CBCT correction could reduce Σ and σof the translational setup and rotational setup, increase the accuracy of SBRT based on VMAT-FFF for patients with spinal metastatic tumors.

Potential contribution of early endothelial progenitor cell (eEPC)-to-macrophage switching in the development of pulmonary plexogenic lesion.

BACKGROUND: Plexiform lesions, which have a dynamic appearance in structure and cellular composition, are the histological hallmark of severe pulmonary arterial hypertension in humans. The pathogenesis of the lesion development remains largely unknown, although it may be related to local inflammation and dysfunction in early progenitor endothelial cells (eEPCs). We tested the hypothesis that eEPCs contribute to the development of plexiform lesions by differentiating into macrophages in the setting of chronic inflammation. METHODS: The eEPC markers CD133 and VEGFR-2, macrophage lineage marker mannose receptor C-type 1 (MRC1), TNFα and nuclear factor erythroid 2-related factor 2 (Nrf2) in plexiform lesions in a broiler model were determined by immunohistochemistry. eEPCs derived from peripheral blood mononuclear cells were exposed to TNFα, and macrophage differentiation and angiogenic capacity of the cells were evaluated by phagocytotic and Matrigel plug assays, respectively. The role of Nrf2 in eEPC-to-macrophage transition as well as in MRC1 expression was also evaluated. Intratracheal installation of TNFα was conducted to determine the effect of local inflammation on the formation of plexiform lesions. RESULTS: Cells composed of the early lesions have a typical eEPC phenotype whereas those in more mature lesions display molecular and morphological characteristics of macrophages. Increased TNFα production in plexiform lesions was observed with lesion progression. In vitro studies showed that chronic TNFα challenge directed eEPCs to macrophage differentiation accompanied by hyperactivation of Nrf2, a stress-responsive transcription factor. Nrf2 activation (Keap1 knockdown) caused a marked downregulation in CD133 but upregulation in MRC1 mRNA. Dual luciferase reporter assay demonstrated that Nrf2 binds to the promoter of MRC1 to trigger its expression. In good agreement with the in vitro observation, TNFα exposure induced macrophage differentiation of eEPCs in Matrigel plugs, resulting in reduced neovascularization of the plugs. Intratracheal installation of TNFα resulted in a significant increase in plexiform lesion density. CONCLUSIONS: This work provides evidence suggesting that macrophage differentiation of eEPCs resulting from chronic inflammatory stimulation contributes to the development of plexiform lesions. Given the key role of Nrf2 in the phenotypic switching of eEPCs to macrophages, targeting this molecular might be beneficial for intervention of plexiform lesions.

Multi-omics research in sarcopenia: Current progress and future prospects.

Sarcopenia is a systemic disease with progressive and generalized skeletal muscle dysfunction defined by age-related low muscle mass, high content of muscle slow fibers, and low muscle function. Muscle phenotypes and sarcopenia risk are heritable; however, the genetic architecture and molecular mechanisms underlying sarcopenia remain largely unclear. In recent years, significant progress has been made in determining susceptibility loci using genome-wide association studies. In addition, recent advances in omics techniques, including genomics, epigenomics, transcriptomics, proteomics, and metabolomics, offer new opportunities to identify novel targets to help us understand the pathophysiology of sarcopenia. However, each individual technology cannot capture the entire view of the biological complexity of this disorder, while integrative multi-omics analyses may be able to reveal new insights. Here, we review the latest findings of multi-omics studies for sarcopenia and provide an in-depth summary of our current understanding of sarcopenia pathogenesis. Leveraging multi-omics data could give us a holistic understanding of sarcopenia etiology that may lead to new clinical applications. This review offers guidance and recommendations for fundamental research, innovative perspectives, and preventative and therapeutic interventions for sarcopenia.

Ionic Hydrogen-Bonded Organic Frameworks for Ion-Responsive Antimicrobial Membranes.

Functionalization of hydrogen-bonded organic frameworks (HOFs) for specific applications has been a long-lasting challenge in HOF materials. Here, an efficient way to integrate functional species in the HOF structure through constructing an anionic framework is presented. The obtained HOFs, taking PFC-33 (PFC = porous materials from FJIRSM,CAS) as an example, integrate a porphyrin photosensitizer as a porous backbone and a commercial biocide as counterions in the structure. The permanent channels and the electrostatic interaction between the framework and the counterions provide PFC-33 ion-responsive biocide-release behavior in various physiological environments, thus exhibiting synergistic photodynamic and chemical antimicrobial efficiency. The unbonded carboxyl groups residing on the HOF surface further allow for manipulating the interfacial interaction between the PFC-33 and the polymer matrix for membrane fabrication. Therefore, a polyHOF membrane with high stability, desired flexibility, and good permeability is obtained, which demonstrates noticeable bacterial inhibition toward Escherichia coli. This study may shed light on the functionalization of HOF materials for broad application potentials.

Dosimetric comparison of accelerated partial breast irradiation and whole breast irradiation with simultaneous integrated boost intensity modulated radiotherapy after breast-conserving surgery for early breast cancer / 肿瘤研究与临床

Objective:To compare the dosimetric differences between accelerated partial breast irradiation intensity modulated radiation therapy (APBI-IMRT) and whole breast irradiation with simultaneous integrated boost intensity modulated radiotherapy (WBI-SIB-IMRT) for early-stage breast cancer after breast-conserving surgery.Methods:A total of 35 patients with early-stage breast cancer in Jilin Province Cancer Hospital between July 2009 and December 2014 after breast-conserving surgery were enrolled. The targeted regions of APBI-IMRT and WBI-SIB-IMRT were created for each patient. The dosimetric difference comparison of the targeted region and normal tissues was evaluated by using dose volume histogram (DVH).Results:There was no significant difference in the dosimetric comparison of gross tumor volume (GTVtb) and planning gross tumor volume (PGTVtb) after correction of cumulative radiation effect (CRE) between WBI-SIB-IMRT group and APBI-IMRT group (both P > 0.05). The dose of clinical target volume (CTV) and planning target volume(PTV) in APBI-IMRT group was higher than that in WBI-SIB-IMRT group [CTV: (4 720±71) cGy vs. (3 889±79) cGy, t = 3.184, P = 0.027; PTV: (4 675±164) cGy vs. (3 807±199) cGy, t = 2.751, P = 0.032] after CRE correction. Compared with WBI-SIB-IMRT group, the dose of ipsilateral lung tissue and left heart tissue in APBI-IMRT group was decreased after CRE correction [(558.5±8.9) cGy vs. (1 304.9±34.4) cGy, t = -7.328, P = 0.001; (35.5±5.3) cGy vs. (843.0±41.5) cGy, t = -8.137, P = 0.001]. V 5/3.6 Gy, V 10/7.3 Gy, V 15/10.9 Gy, V 20/14.6 Gy, V 25/18.2 Gy and V 30/21.9 Gy of the ipsilateral lung and V 30/21.9Gy, V 40/29.2Gy of left heart in all breast cancer patients after two chemotherapy treatments had significant differences (all P = 0.001). Conclusion:Compared with WBI-SIB, APBI-IMRT can improve the dose distribution in target area and reduce the volume of high dose irradiation in organs at risk.

Difference analysis of results of disease risk assessment by using binary Logistic regression under different analysis strategies / 中华检验医学杂志

Objective To investigate the importance of conditional control on the results of binary Logistic regression analysis.Methods 664 male patients diagnosed with CHD and 400 healthy controls who visited the Department of Cardiology at People's Hospital of Yuxi City in Yunnan province from October 2010 to March 2013were enrolled consecutively in this case-control study, and 14 physiological and biochemical indexes[including:age,UA,TC,TG,HDL-C,LDL-C,APOA1,APOB100,Lp(a),HCY, TBIL,DBIL,IBIL,γ-GT]were collected.The correlations and differences in mathematical model results between physiological,biochemical indexes and CHD were compared by binary Logistic regression analysis under different statistical analysis strategies and then the model was analyzed by the ROC curve.Results (1)With no conditional control,all of the 14 physiological and biochemical indexes were directly inputted in the binary Logistic regression analysis,and after 11 steps regression analysis,11 indexes[age,UA,TG, HDL-C,LDL-C,APOA1,APOB100, Lp(a), HCY, DBIL, γ-GT]were retained.Because of the self-correcting ability of the binary Logistic regression analysis, relatively satisfactory results can be obtained. However,someof the resultsarehard to explain.(2)According to the application conditions of Logistic regression analysis,after performing the normality test, difference analysis and correlation analysis of these indexes, using condition analysis and control, considering the distribution characteristics of the indexes, excluding internal confounding factors among variables,9 more independent indexes[age,UA,TC,lnTG, lnLp(a),lnHCY,HDL-C,LDL-C and TBIL]were selected for Logistic regression analysis.After 7 steps regression analysis,7 indexes[age, UA, HDL-C, lnTG, lnLp(a), lnHCY and lnTBIL]were finally selected,and the area under the curve is 0.927.Conclusion When the binary Logistic regression analysis was used to confirm risk factors and establish risk assessment models for complex diseases, it is better to adopt strict conditional control to improve the reliability and validity of the analysis.

Efficacy analysis of accelerated partial breast irradiation versus whole breast irradiation with simultaneous integrated boost after breast-conserving surgery for early-stage breast cancer / 中华放射医学与防护杂志

Objective To evaluate the efficacy of accelerated partial breast irradiation ( APBI ) and whole breast irradiation ( WBI ) with simultaneous integrated boost ( SIB ) from the perspective of economics, and provide a reference for postoperative adjuvant therapy mode selection for early-stage breast cancer after breast-conserving surgery. Methods A total of 355 early-stage breast cancer patients who underwent APBI or WBI-SIB after breast-conserving surgery were evaluated on efficacy and cost-effectiveness, of which 177 patients received APBI, and 178 patients received WBI-SIB. Survival analysis was done according to treatment received. NCI-CTC 3.0 was used to score the toxicities. Breast aesthetic outcome were evaluated with Harris standards. Results Median follow-up was 42 months ( 5.8 -92.7 months) . The 3-year locoregional recurrence free survival( LRFS) rates in APBI group and WBI-SIB group were 98.2％ and 97.6％, distant metastasis free survival( DMFS) were 94.3％ and 93.7％, disease-free survival ( DFS) were 93.1％ and 91.6％, and overall survival 95.5％ and 94.3％, respectively, without statistically significant differences(P>0.05). Compared with WBI-SIB group, the acute reaction rates in APBI group decreased from 5. 6％ to 3.4％(χ2 =6.044, P <0. 05), and late reactions from 5.6％ to 2.3％ (χ2 =6.149, P<0. 05), while the cosmetic outcome improved from 88.8％ to 93.8％(χ2 =5.22, P<0. 05). Moreover, the processing average time was shortened by 26.5 d (χ2 =40.76, P<0. 05). Conclusions After breast-conserving surgery, the efficacy of APBI showed no difference from WBI-SIB with respect to 3-year local control, disease-free survival, and overall survival, but displayed a significantly better toxicity profile and cost-effectiveness ratio for early breast cancer patients. It can be used as a good radiotherapy model after breast-conserving surgery in early-stage breast cancer.

Characteristics and Impact Factors of Renal Threshold for Glucose Excretion in Patients with Type 2 Diabetes Mellitus

Sodium glucose co-transporter 2 (SGLT-2) inhibitors are newly developed but promising medicine for type 2 diabetes. However, patients with a different renal threshold for glucose excretion (RT(G)) may have a different reaction to this medicine. Therefore, the objective of this study was to investigate the characteristics of RT(G) and its impact factors in patients with type 2 diabetes mellitus (T2DM). The clinical and laboratory data of 36 healthy individuals and 168 in-hospital patients with T2DM were collected and analyzed, RTG was calculated using blood glucose (BG) measured by dynamic BG monitoring, urinary glucose excretion (UGE) and estimated glomerular filtration rate (eGFR). The characteristics of RT(G) were investigated. The risk factors for high RT(G) were analyzed using non-conditional logistic regression analysis. Our results found that RT(G) of the T2DM group was higher than that of the healthy individuals (P < 0.05); and 22.22% from the healthy individuals group but 58.33% from the T2DM group had high RT(G). Age, duration of diabetes, body mass index (BMI), and homeostasis model assessment insulin resistance index (HOMA-IR) were independently associated with high RT(G) (P < 0.05). Further stratified analysis revealed that RT(G) in T2DM patients increased with age, duration of diabetes, and BMI. In conclusion, RT(G) is increased in patients with T2DM, especially in those with longer diabetic duration, higher BMI, and those who are older. Therefore, these patients may be more sensitive to SGLT-2 inhibitors.

Resveratrol-downregulated phosphorylated liver kinase B1 is involved in senescence of acute myeloid leukemia stem cells.

Senescence is an important obstacle to cancer development. Engaging a senescent response may be an effective way to cure acute myeloid leukemia (AML). The aim of this study was to examine the effect of resveratrol-downregulated phosphorylated liver kinase B1 (pLKB1) on the senescence of acute myeloid leukemia (AML) stem cells. The protein expressions of pLKB1 and Sirtuin 1 (SIRT1), a regulator of pLKB1, were measured in CD34(+)CD38(-) KG1a cells treated with resveratrol (40 µmol/L) or not by Western blotting. Senescence-related factors were examined, including p21 mRNA tested by real-time PCR, cell morphology by senescence-associated ß-galactosidase (SA-ß-gal) staining, cell proliferation by MTT assay and cell cycle by flow cytometry. Besides, apoptosis was flow cytometrically determined. The results showed that pLKB1 was highly expressed in CD34(+)CD38(-) KG1a cells, and resveratrol, which could downregulate pLKB1 through activation of SIRT1, induced senescence and apoptosis of CD34(+)CD38(-) KG1a cells. It was concluded that resveratrol-downregulated pLKB1 is involved in the senescence of AML stem cells.

Resveratrol-downregulated phosphorylated liver kinase B1 is involved in senescence of acute myeloid leukemia stem cells / 华中科技大学学报（医学）（英德文版）

Senescence is an important obstacle to cancer development. Engaging a senescent response may be an effective way to cure acute myeloid leukemia (AML). The aim of this study was to examine the effect of resveratrol-downregulated phosphorylated liver kinase B1 (pLKB1) on the senescence of acute myeloid leukemia (AML) stem cells. The protein expressions of pLKB1 and Sirtuin 1 (SIRT1), a regulator of pLKB1, were measured in CD34(+)CD38(-) KG1a cells treated with resveratrol (40 μmol/L) or not by Western blotting. Senescence-related factors were examined, including p21 mRNA tested by real-time PCR, cell morphology by senescence-associated β-galactosidase (SA-β-gal) staining, cell proliferation by MTT assay and cell cycle by flow cytometry. Besides, apoptosis was flow cytometrically determined. The results showed that pLKB1 was highly expressed in CD34(+)CD38(-) KG1a cells, and resveratrol, which could downregulate pLKB1 through activation of SIRT1, induced senescence and apoptosis of CD34(+)CD38(-) KG1a cells. It was concluded that resveratrol-downregulated pLKB1 is involved in the senescence of AML stem cells.

Effects of iodine excess on TPO and NIS genes mRNA expression in rats / 中国地方病学杂志

Objective To observe the effects of iodine excess on thyroid morphology,the expression of thyroid peroxidase and sodium iodide symporter mRNA and to explore their mechanisms.Methods One-month SD rats were divided into three groups:control iodine(CI),high iodine Ⅰ(HI Ⅰ)and high iodineⅡ(HI Ⅱ)and were fed with water containing iodine in different concentrations by adding K103(5,5000,10 000μg/L)respectively.Rats were sacrificed after being fed for six months.The morphology of thyroid was investigated under light microscopy and electron microscopy,the serum thyroid hormones and ratio of TPO/β-actin and NIS/β-actin were measured by radio-immunoassay and RT-PCR method.Results The major changes were increased follicles with colloid accumulation in HI groups.The levels of serum thyroid hormones TT3 and TT4 were decreased gradually from CI[(75.68±13.99,1.45±0.49)nmol/L]to HI Ⅰ[(73.82±16.48,1.34±0.31)nmol/L]and HIⅡ groups[(70.65±11.43,1.15±0.39)nmol/L],but there were no significant differences among three groups(F=O.371,l.163,P＞0.05).The TPO and NIS mRNA expressions in HI Ⅰ(1.28±0.10,0.56±O.17)and HI Ⅱ(1.14±0.04,0.39±0.06)were significantly lower(F=30.863,62.62.675,P＜O.05)than those of control group(1.39±0.08,0.71±0.13).Conclusions Chronic iodine excess leads to definite histological changes in rat thyroid,and inhibits the expressions of TPO and NIS mRNA as well as thyroid hormone synthesis,which in turn acts as a protective mechanism against iodine excess.