Abstract The incidence of non-alcoholic fatty liver (NAFLD) remains high, and many NAFLD patients suffer from severe ischemia-reperfusion injury (IRI). Currently, no practical approach can be used to treat IRI. Puerarin plays a vital role in treating multiple diseases, such as NAFLD, stroke, diabetes, and high blood pressure. However, its role in the IRI of the fatty liver is still unclear. We aimed to explore whether puerarin could protect the fatty liver from IRI. C57BL/6J mice were fed with a high‐fat diet (HFD) followed by ischemia reperfusion injury. We showed that hepatic IRI was more severe in the fatty liver compared with the normal liver, and puerarin could significantly protect the fatty liver against IRI and alleviate oxidative stress. The PI3K-AKT signaling pathway was activated during IRI, while liver steatosis decreased the level of activation. Puerarin significantly protected the fatty liver from IRI by reactivating the PI3K-AKT signaling pathway. However, LY294002, a PI3K-AKT inhibitor, attenuated the protective effect of puerarin. In conclusion, puerarin could significantly protect the fatty liver against IRI by activating the PI3K-AKT signaling pathway. nonalcoholic non alcoholic (NAFLD ischemiareperfusion . (IRI) Currently diseases stroke diabetes pressure However unclear C57BL6J CBLJ C57BL 6J C BL J highfat fat HFD (HFD stress PI3KAKT PIKAKT PI3K AKT PI K activation LY294002 LY inhibitor conclusion (IRI CBL KAKT PIK LY29400 LY2940 LY294 LY29 LY2

Abstract MCH1 is a synthetic macamide that has shown in vitro inhibitory activity on fatty acid amide hydrolase (FAAH), an enzyme responsible for endocannabinoid metabolism. This inhibition can modulate endocannabinoid and dopamine signaling in the nucleus accumbens (NAc), potentially having an antidepressant-like effect. The present study aimed to evaluate the effect of the in vivo administration of MCH1 (3, 10, and 30 mg/kg, ip) in 2-month-old BALB/c male mice (n=97) on forced swimming test (FST), light-dark box (LDB), and open field test (OFT) and on early gene expression changes 2 h after drug injection related to the endocannabinoid system (Cnr1 and Faah) and dopaminergic signaling (Drd1 and Drd2) in the NAc core. We found that the 10 mg/kg MCH1 dose reduced the immobility time compared to the vehicle group in the FST with no effect on anxiety-like behaviors measured in the LDB or OFT. However, a 10 mg/kg MCH1 dose increased locomotor activity in the OFT compared to the vehicle. Moreover, RT-qPCR results showed that the 30 mg/kg MCH1 dose increased Faah gene expression by 2.8-fold, and 10 mg/kg MCH1 increased the Cnr1 gene expression by 4.3-fold compared to the vehicle. No changes were observed in the expression of the Drd1 and Drd2 genes in the NAc at either MCH1 dose. These results indicated that MCH1 might have an antidepressant-like effect without an anxiogenic effect and induces significant changes in endocannabinoid-related genes but not in genes of the dopaminergic signaling system in the NAc of mice. MCH FAAH, FAAH , (FAAH) metabolism NAc, (NAc) antidepressantlike antidepressant like 3, 3 (3 mgkg mg kg ip 2monthold monthold month old BALBc BALB c n=97 n97 n 97 (n=97 FST, (FST) lightdark light dark LDB, (LDB) (OFT Cnr (Cnr Drd (Drd core 1 anxietylike anxiety However Moreover RTqPCR RT qPCR 2.8fold, 28fold fold 2.8 fold, 8 2.8-fold 4.3fold 43fold 4.3 4 endocannabinoidrelated (FAAH (NAc ( n=9 n9 9 (n=9 (FST (LDB 8fold 2.8fold 28 2. 3fold 43 4. n= (n= (n

Abstract The aim of this study was to explore the association between differential percentages of dendritic cell (DC) subsets in peripheral blood and malignancy (grade and lymph node metastasis) of peritoneal adenocarcinoma patients and the frequencies of dendritic cell subsets in the normal controls. The peripheral blood of 30 patients with peritoneal adenocarcinoma and 12 healthy controls were collected for multicolor flow cytometry analysis. Peritoneal adenocarcinoma patients were grouped according to the malignant degree (grade and lymph node metastasis). Percentages of myeloid DCs (mDCs) and its subsets MDC1 and MDC2 in DCs were lower in peripheral blood of patients with peritoneal adenocarcinoma than in normal controls. The percentages of plasmacytoid dendritic cells (pDCs) and CD16+mDCs in DCs were higher than in normal controls. Compared with poor differentiation grade, patients with well/moderate differentiation grade had an increased percentage of CD16+mDCs. Contrary to CD16+mDCs, the percentage of MDC1 was lower in the well/moderate differentiation grade group. In patients with no lymph node metastasis, pDCs and CD16+mDCs levels were higher compared with patients with lymph node metastasis. mDCs and MDC1 levels had opposite results. pDCs were positively correlated with CD16+mDCs in peripheral blood of peritoneal patients, as was mDCs and MDC1. CD16+mDCs were negatively correlated with MDC1. The percentages of pDCs and CD16+mDCs in DCs were positively correlated with CD3+CD8+T cells, and pDCs also positively correlated with CD8+PD-1+T cells. Our results revealed that DCs subsets correlated with peritoneal adenocarcinoma malignancy. Dendritic cells play an independent role in the immune function of peritoneal adenocarcinoma. DC (DC metastasis 3 1 analysis . (mDCs MDC (pDCs CD16mDCs CDmDCs CD16 CD wellmoderate well moderate group CD3CD8T CDCDT CD3 CD8 T CD8+PD1+T CD8PD1T CDPDT CD8+PD 1+T PD CD1 PD1 CD8PD CDPD 1T

Abstract The cure rates for osteosarcoma have remained unchanged in the past three decades, especially for patients with pulmonary metastasis. Thus, a new and effective treatment for metastatic osteosarcoma is urgently needed. Anlotinib has been reported to have antitumor effects on advanced osteosarcoma. However, both the effect of anlotinib on autophagy in osteosarcoma and the mechanism of anlotinib-mediated autophagy in pulmonary metastasis are unclear. The effect of anlotinib treatment on the metastasis of osteosarcoma was investigated by transwell assays, wound healing assays, and animal experiments. Related proteins were detected by western blotting after anlotinib treatment, ATG5 silencing, or ATG5 overexpression. Immunofluorescence staining and transmission electron microscopy were used to detect alterations in autophagy and the cytoskeleton. Anlotinib inhibited the migration and invasion of osteosarcoma cells but promoted autophagy and increased ATG5 expression. Furthermore, the decreases in invasion and migration induced by anlotinib treatment were enhanced by ATG5 silencing. In addition, Y-27632 inhibited cytoskeletal rearrangement, which was rescued by ATG5 overexpression. ATG5 overexpression enhanced epithelial-mesenchymal transition (EMT). Mechanistically, anlotinib-induced autophagy promoted migration and invasion by activating EMT and cytoskeletal rearrangement through ATG5 both in vitro and in vivo. Our results demonstrated that anlotinib can induce protective autophagy in osteosarcoma cells and that inhibition of anlotinib-induced autophagy enhanced the inhibitory effects of anlotinib on osteosarcoma metastasis. Thus, the therapeutic effect of anlotinib treatment can be improved by combination treatment with autophagy inhibitors, which provides a new direction for the treatment of metastatic osteosarcoma. decades Thus needed However anlotinibmediated mediated unclear assays experiments ATG silencing cytoskeleton expression Furthermore addition Y27632 Y 27632 Y-2763 epithelialmesenchymal epithelial mesenchymal EMT. . (EMT) Mechanistically anlotinibinduced vivo inhibitors Y2763 2763 Y-276 (EMT Y276 276 Y-27 Y27 27 Y-2 Y2 2 Y-

Abstract The aim of this study was to evaluate the association between diabetes and cognitive performance in a nationally representative study in Brazil. We also aimed to investigate the interaction between frailty and diabetes on cognitive performance. A cross-sectional analysis of the Brazilian Longitudinal Study of Aging (ELSI-Brazil) baseline data that included adults aged 50 years and older was conducted. Linear regression models were used to study the association between diabetes and cognitive performance. A total of 8,149 participants were included, and a subgroup analysis was performed in 1,768 with hemoglobin A1c data. Diabetes and hemoglobin A1c levels were not associated with cognitive performance. Interaction of hemoglobin A1c levels with frailty status was found on global cognitive z-score (P-value for interaction=0.038). These results suggested an association between higher hemoglobin A1c levels and lower cognitive performance only in non-frail participants. Additionally, undiagnosed diabetes with higher hemoglobin A1c levels was associated with both poor global cognitive (β=-0.36; 95%CI: -0.62; -0.10, P=0.008) and semantic verbal fluency performance (β=-0.47; 95%CI: -0.73; -0.21, P=0.001). In conclusion, higher hemoglobin A1c levels were associated with lower cognitive performance among non-frail participants. Higher hemoglobin A1c levels without a previous diagnosis of diabetes were also related to poor cognitive performance. Future longitudinal analyses of the ELSI-Brazil study will provide further information on the role of frailty in the association of diabetes and glycemic control with cognitive decline. Brazil crosssectional cross sectional ELSIBrazil ELSI (ELSI-Brazil 5 conducted 8149 8 149 8,14 1768 1 768 1,76 Ac c zscore z score Pvalue P value interaction=0.038. interaction0038 interaction=0.038 . 0 038 interaction=0.038) nonfrail non frail Additionally β=0.36 β036 β β= 0.36 36 (β=-0.36 95%CI 95CI CI 95 0.62 062 62 -0.62 0.10, 010 10 -0.10 P=0.008 P0008 008 β=0.47 β047 0.47 47 (β=-0.47 0.73 073 73 -0.73 0.21, 021 21 -0.21 P=0.001. P0001 P=0.001 001 P=0.001) conclusion decline 814 14 8,1 176 76 1,7 interaction003 interaction=0.03 03 β=0.3 β03 036 0.3 3 (β=-0.3 9 0.6 06 6 -0.6 0.10 01 -0.1 P=0.00 P000 00 β=0.4 β04 047 0.4 4 (β=-0.4 0.7 07 7 -0.7 0.21 02 2 -0.2 81 8, 17 1, interaction00 interaction=0.0 β=0. β0 0. (β=-0. -0. 0.1 P=0.0 P00 04 0.2 interaction0 interaction=0. β=0 (β=-0 -0 P=0. P0 interaction=0 (β=- - P=0 interaction= (β= P= (β

The treatment of arterial hypertension (AH) contributes to the reduction of morbidity and mortality. Gender differences are likely to play a role, as non-treatment is associated with clinical and sociodemographic aspects. The aim of this study was to investigate the factors associated with non-treatment of AH and gender differences in hypertensive individuals from the ELSA-Brasil cohort. The study was conducted with 5,743 baseline hypertensive cohort participants. AH was considered if there was a previous diagnosis or if systolic blood pressure (SBP) was ≥140 and/or diastolic BP (DBP) was ≥90 mmHg. Sociodemographic and anthropometric data, lifestyle, comorbidities, and use of antihypertensive medications were evaluated through interviews and in-person measurements. Treatment with renin-angiotensin-aldosterone system inhibitors (RAASi) or other antihypertensive medications and non-treatment were evaluated with multivariate logistic regression. Non-treatment was observed in 32.8% of hypertensive individuals. Of the 67.7% treated individuals, 41.1% received RAASi. Non-treatment was associated with alcohol consumption in women (OR=1.41; 95%CI: 1.15-1.73; P=0.001), lowest schooling level in men (OR=1.70; 95%CI: 1.32-2.19; P<0.001), and younger age groups in men and women (strongest association in males aged 35-44 years: OR=4.58, 95%CI: 3.17-6.6, P<0.001). Among those using RAASi, a higher proportion of white, older individuals, and with more comorbidities was observed. The high percentage of non-treatment, even in this civil servant population, indicated the need to improve the treatment cascade for AH. Public health policies should consider giving special attention to gender roles in groups at higher risk of non-treatment to reduce inequities related to AH in Brazil. (AH mortality role nontreatment non aspects ELSABrasil ELSA Brasil 5743 5 743 5,74 participants SBP (SBP 140 ≥14 andor DBP (DBP 90 ≥9 mmHg data lifestyle inperson person measurements reninangiotensinaldosterone renin angiotensin aldosterone RAASi (RAASi regression Nontreatment Non 328 32 8 32.8 677 67 7 67.7 411 41 1 41.1 OR=1.41 OR141 OR (OR=1.41 95%CI 95CI CI 95 1.151.73 115173 1.15 1.73 15 73 1.15-1.73 P=0.001, P0001 P P=0.001 , 0 001 P=0.001) OR=1.70 OR170 70 (OR=1.70 1.322.19 132219 1.32 2.19 2 19 1.32-2.19 P<0.001, P<0.001 P<0.001) strongest 3544 35 44 35-4 years OR458 4 58 OR=4.58 3.176.6, 31766 3.17 6.6, 3 17 6 3.17-6.6 P<0.001. . white nontreatment, treatment, population Brazil 574 74 5,7 14 ≥1 9 ≥ 32. 67. 41. OR=1.4 OR14 (OR=1.4 151 1.151.7 11517 115 1.1 173 1.7 1.15-1.7 P000 P=0.00 00 OR=1.7 OR17 (OR=1.7 322 1.322.1 13221 132 1.3 219 2.1 1.32-2.1 P<0.00 354 35- OR45 OR=4.5 176 3.176.6 3176 317 3.1 66 6.6 3.17-6. 57 5, OR=1. OR1 (OR=1. 1.151. 1151 11 1. 1.15-1. P00 P=0.0 1.322. 1322 13 21 2. 1.32-2. P<0.0 OR4 OR=4. 3.176. 31 3. 6. 3.17-6 OR=1 (OR=1 1.151 1.15-1 P0 P=0. 1.322 1.32-2 P<0. OR=4 3.176 3.17- OR= (OR= 1.15- P=0 1.32- P<0 (OR P= P<

“Penumbra sign” is a characteristic finding in magnetic resonance imaging (MRI) of Brodie's abscess, a rare variant of subacute osteomyelitis. We aimed to discuss the imaging finding penumbra sign that will help in the diagnosis of osteomyelitis and may be useful to clinicians in differential diagnosis. A 26-year-old male patient presented to the emergency department with complaints of pain and limping in the right knee that did not go away. He had a history of arthroscopic debridement and percutaneous fixation surgery due to osteochondral fragment 3 years ago. There were no additional findings in the patient's vital parameters, physical examination, and medical history. X-ray imaging revealed two screws in the distal femur and a well-defined sclerotic rim surrounding a radiolucent lesion anterior to the screws. MRI revealed a lesion in the distal femoral metaphysis with low-density fluid and hyperintense granulation tissue surrounding it. After surgical abscess drainage and local debridement, bone cement was placed in the resulting cavity. Teicoplanin treatment was started. The patient was discharged and complete recovery was achieved in the second month. The diagnosis of osteomyelitis is often missed or confused with bone tumors in non-traumatic cases presenting with persistent bone pain. MRI imaging is frequently used in differential diagnosis, and detection of characteristic imaging signs such as the penumbra sign accelerates the diagnosis. In this context, emergency department clinicians, in particular, should be cautious and not forget that early treatment can be started by recognizing these signs. Penumbra (MRI Brodies Brodie s 26yearold yearold 26 year old away ago patients parameters examination Xray X ray welldefined well defined lowdensity low density it cavity month nontraumatic non traumatic context particular 2

This study aimed to analyze the safety and applicability of a 90-min duration of infusion (SDI) of obinutuzumab in patients with B-cell non-Hodgkin's lymphoma (NHL) in a tertiary hospital in China. This exploratory clinical trial was performed at Jiangsu Province Hospital. All patients were treated with the standard infusion regimen for the first infusion. If no grade ≥3 infusion-related reactions (IRRs) occurred, the subsequent infusions were given as SDI. The primary endpoint was the incidence of IRR during the standard infusion (3-4 h) and 90-min SDI regimens. This study enrolled 208 patients and all completed cycle 1. Forty-one patients (19.71%) had IRRs: five (2.40%) with grade 1, twenty-eight (13.46%) with grade 2, and eight (3.85%) with grade 3. The 41 patients had 71 IRRs, mainly fever (40.85%), chest pain/tightness (12.68%), and dyspnea (9.86%). The occurrence of IRRs in the first infusion was significantly lower in patients who received oral acetaminophen prophylaxis than those who did not (10.72% vs 30.21%, P<0.001). For the subsequent cycles with 90-min SDI, only two (0.25%) IRRs occurred among 814 infusions (one grade 1 hand numbness and one grade 2 chill/fever). The 90-min obinutuzumab SDI might be safe and feasible in patients with B-cell NHL in China. 90min min 90 (SDI Bcell B cell nonHodgkins non Hodgkin s (NHL China Hospital 3 ≥ infusionrelated related (IRRs 34 4 (3- h regimens 20 Fortyone Forty 19.71% 1971 19 (19.71% 2.40% 240 40 (2.40% twentyeight twenty 13.46% 1346 13 46 (13.46% 3.85% 385 85 (3.85% 7 40.85%, 4085 40.85% , (40.85%) paintightness pain tightness 12.68%, 1268 12.68% 12 68 (12.68%) 9.86%. 986 9.86% . 9 86 (9.86%) 10.72% 1072 10 72 (10.72 3021 30 21 30.21% P<0.001. P0001 P P<0.001 0 001 P<0.001) 0.25% 025 25 (0.25% 81 chill/fever. chillfever chill/fever chill chill/fever) (3 19.71 197 (19.71 2.40 24 (2.40 13.46 134 (13.46 3.85 38 8 (3.85 408 40.85 (40.85% 126 12.68 6 (12.68% 98 9.86 (9.86% 10.72 107 (10.7 302 30.21 P000 P<0.00 00 0.25 02 (0.25 ( 19.7 (19.7 2.4 (2.4 13.4 (13.4 3.8 (3.8 40.8 (40.85 12.6 (12.68 9.8 (9.86 10.7 (10. 30.2 P00 P<0.0 0.2 (0.2 19. (19. 2. (2. 13. (13. (3. 40. (40.8 12. (12.6 9. (9.8 10. (10 30. P0 P<0. 0. (0. (19 (2 (13 (40. (12. (9. (1 P<0 (0 (40 (12 (9 P< (4

This study was conducted to evaluate how sterubin affects rotenone-induced Parkinson's disease (PD) in rats. A total of 24 rats were distributed into 4 equal groups: normal saline control and rotenone control were administered saline or rotenone (ROT), respectively, orally; sterubin 10 received ROT + sterubin 10 mg/kg po; and sterubin alone was administered to the test group (10 mg/kg). Rats of the normal saline and sterubin alone groups received sunflower oil injection (sc) daily, 1 h after receiving the treatments cited above, while rats of the other groups received rotenone injection (0.5 mg/kg, sc). The treatment was continued over the course of 28 days daily. On the 29th day, catalepsy and akinesia were assessed. The rats were then euthanized, and the brain was extracted for estimation of endogenous antioxidants (MDA: malondialdehyde, GSH: reduced glutathione, CAT: catalase, SOD: superoxide dismutase), nitrative (nitrite) stress markers, neuroinflammatory cytokines, and neurotransmitter levels and their metabolites (3,4-dihydroxyphenylacetic acid (DOPAC), dopamine (DA), norepinephrine (NE), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA)). Akinesia and catatonia caused by ROT reduced the levels of endogenous antioxidants (GSH, CAT, and SOD), elevated the MDA level, and altered the levels of nitrites, neurotransmitters, and their metabolites. Sterubin restored the neurobehavioral deficits, oxidative stress, and metabolites of altered neurotransmitters caused by ROT. Results demonstrated the anti-Parkinson's activities of sterubin in ROT-treated rats. rotenoneinduced induced Parkinsons Parkinson s PD (PD 2 ROT, , (ROT) respectively orally mgkg mg kg po (1 mg/kg. . mg/kg) sc (sc daily above 0.5 05 0 5 (0. sc. sc) th day assessed euthanized (MDA malondialdehyde GSH glutathione CAT catalase SOD dismutase, dismutase dismutase) nitrite (nitrite markers cytokines 3,4dihydroxyphenylacetic 34dihydroxyphenylacetic dihydroxyphenylacetic 3,4 3 DOPAC, DOPAC (DOPAC) DA, DA (DA) NE, NE (NE) 5HT, 5HT HT (5-HT) 5hydroxyindoleacetic hydroxyindoleacetic 5HIAA, 5HIAA HIAA (5-HIAA) HVA. HVA (HVA)) GSH, (GSH SOD, SOD) level nitrites deficits antiParkinsons anti ROTtreated treated (ROT ( 0. (0 4dihydroxyphenylacetic 34 3, (DOPAC (DA (NE (5-HT (5-HIAA (HVA) (HVA

Abstract We aimed to develop a prognostic model for primary pontine hemorrhage (PPH) patients and validate the predictive value of the model for a good prognosis at 90 days. A total of 254 PPH patients were included for screening of the independent predictors of prognosis, and data were analyzed by univariate and multivariable logistic regression tests. The cases were then divided into training cohort (n=219) and validation cohort (n=35) based on the two centers. A nomogram was developed using independent predictors from the training cohort to predict the 90-day good outcome and was validated from the validation cohort. Glasgow Coma Scale score, normalized pixels (used to describe bleeding volume), and mechanical ventilation were significant predictors of a good outcome of PPH at 90 days in the training cohort (all P<0.05). The U test showed no statistical difference (P=0.892) between the training cohort and the validation cohort, suggesting the model fitted well. The new model showed good discrimination (area under the curve=0.833). The decision curve analysis of the nomogram of the training cohort indicated a great net benefit. The PPH nomogram comprising the Glasgow Coma Scale score, normalized pixels, and mechanical ventilation may facilitate predicting a 90-day good outcome. (PPH 9 25 tests n=219 n219 n 219 (n=219 n=35 n35 35 (n=35 centers 90day day score used volume, volume , volume) all P<0.05. P005 P P<0.05 . 0 05 P<0.05) P=0.892 P0892 892 (P=0.892 well area curve=0.833. curve0833 curve=0.833 833 curve=0.833) benefit 2 n=21 n21 21 (n=21 n=3 n3 3 (n=3 P00 P<0.0 P=0.89 P089 89 (P=0.89 curve083 curve=0.83 83 n=2 n2 (n=2 n= (n= P0 P<0. P=0.8 P08 8 (P=0.8 curve08 curve=0.8 (n P<0 P=0. (P=0. curve0 curve=0. P< P=0 (P=0 curve=0 P= (P= curve= (P

Abstract Sarcopenia is a pathology resulting from a progressive and severe loss of muscle mass, strength, and function in the course of aging, which has deleterious consequences on quality of life. Among the most widespread studies on the issue are those focused on the effect of different types of physical exercise on patients with sarcopenia. This randomized controlled study aimed to compare the effects of a whole-body vibration exercise (WBV) session on the inflammatory parameters of non-sarcopenic (NSG, n=22) and sarcopenic elderly (SG, n=22). NSG and SG participants were randomly divided into two protocols: intervention (squat with WBV) and control (squat without WBV). After a one-week washout period, participants switched protocols, so that everyone performed both protocols. Body composition was assessed by dual-energy radiological absorptiometry (DXA) and function through the six-minute walk test (6MWD) and Short Physical Performance Battery (SPPB). Plasma soluble tumor necrosis factor receptors (sTNFR) were determined by enzyme-linked immunosorbent assay (ELISA) and measured before and immediately after each protocol. After exercise with WBV, there was an increase in sTNFR2 levels in the NSG (P<0.01; d=-0.69 (-1.30; -0.08) and SG (P<0.01, d=-0.95 (-1.57; -0.32) groups. In conclusion, an acute session of WBV influenced sTNFr2 levels, with sarcopenic individuals showing a greater effect. This suggested that WBV had a more pronounced impact on sTNFr2 in those with loss of muscle strength and/or physical performance. Additionally, WBV is gaining recognition as an efficient strategy for those with persistent health issues. mass aging life sarcopenia wholebody whole body (WBV nonsarcopenic non NSG, (NSG n=22 n22 n 22 SG, (SG n=22. . protocols squat WBV. oneweek one week period dualenergy dual energy DXA (DXA sixminute six minute 6MWD MWD (6MWD SPPB. SPPB (SPPB) sTNFR (sTNFR enzymelinked enzyme linked ELISA (ELISA protocol P<0.01 P001 P 0 01 (P<0.01 d=0.69 d069 d d= 0.69 69 d=-0.6 1.30 130 1 30 (-1.30 0.08 008 08 -0.08 P<0.01, d=0.95 d095 0.95 95 d=-0.9 1.57 157 57 (-1.57 0.32 032 32 -0.32 groups conclusion sTNFr andor or performance Additionally issues n=2 n2 2 (SPPB P<0.0 P00 (P<0.0 d=0.6 d06 069 0.6 6 d=-0. 1.3 13 3 (-1.3 0.0 00 -0.0 d=0.9 d09 095 0.9 9 1.5 15 5 (-1.5 0.3 03 -0.3 n= P<0. P0 (P<0. d=0. d0 06 0. d=-0 1. (-1. -0. 09 P<0 (P<0 d=0 d=- (-1 -0 P< (P< (- - (P (

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, with approximately 600,000 new cases each year. A small number of HNSCCs are caused by human papillomavirus (HPV) infection. Frizzled related protein (FRZB) has been reported in many inflammatory diseases and cancers, but it is yet unclear how FRZB affects HNSCC, as well as its role and underlying mechanism. TIMER2 database was utilized to evaluate FRZB expression in cancer tissues, and FRZB expression in HNSCC tissues was confirmed by samples obtained from Gene Expression Omnibus. To identify whether FRZB could be used as a prognostic predictor, we performed univariate and multivariate Cox regression analyses. FRZB co-expression profile was explored using the LinkedOmics database, then Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses were performed for these FRZB-related genes in HNSCC samples. Lasso regression analysis was subsequently used to screen for prognostic variables, and we determined the infiltration of immune cells in HNSCC patients to clarify the influence of FRZB on tumor immune microenvironment. At last, we assessed the association between FRZB expression and immune checkpoint gene, and compared the sensitivity of common chemotherapeutic agents. In this study, we found that FRZB was dysregulated in HNSCC tumor tissues and had a relationship with clinical parameters. The reliability and independence of FRZB as a factor in determining a patient's prognosis for HNSCC was also established. Additional investigation revealed that FRZB was linked to common immune checkpoint genes and may be implicated in immune infiltration. (HNSCC worldwide 600000 600 000 600,00 year HPV (HPV infection (FRZB cancers mechanism TIMER Omnibus predictor coexpression co FRZBrelated variables microenvironment last gene agents study parameters patient s established 60000 60 00 600,0 6000 6 0 600,

Arthritis has important cardiovascular repercussions. Phenylephrine-induced vasoconstriction is impaired in rat aortas in the early phase of the adjuvant-induced arthritis (AIA), around the 15th day post-induction. Therefore, the present study aimed to verify the effects of AIA on hyporesponsiveness to phenylephrine in rat aortas. AIA was induced by intradermal injection of Mycobacterium tuberculosis (3.8 mg/dL) in the right hind paw of male Wistar rats (n=27). Functional experiments in isolated aortas were carried out 15 days after AIA induction. Morphometric and stereological analyses of the aortas were also performed 36 days after the induction of AIA. AIA did not promote structural modifications in the aortas at any of the time points studied. AIA reduced phenylephrine-induced contraction in endothelium-intact aortas, but not in endothelium-denuded aortas. However, AIA did not change KCl-induced contraction in either endothelium-intact or denuded aortas. L-NAME (non-selective NOS inhibitor), 1400W (selective iNOS inhibitor), and ODQ (guanylyl cyclase inhibitor) reversed AIA-induced hyporesponsiveness to phenylephrine in intact aortas. 7-NI (selective nNOS inhibitor) increased the contraction induced by phenylephrine in aortas from AIA rats. In summary, the hyporesponsiveness to phenylephrine induced by AIA was endothelium-dependent and mediated by iNOS-derived NO through activation of the NO-guanylyl cyclase pathway. repercussions Phenylephrineinduced Phenylephrine adjuvantinduced adjuvant AIA, , (AIA) th postinduction. postinduction post post-induction Therefore 3.8 38 3 8 (3. mg/dL mgdL mg dL n=27. n27 n n=27 . 27 (n=27) 1 studied phenylephrineinduced endotheliumintact endothelium endotheliumdenuded However KClinduced KCl LNAME L NAME nonselective non selective inhibitor, inhibitor W guanylyl AIAinduced 7NI NI 7 summary endotheliumdependent dependent iNOSderived derived NOguanylyl pathway (AIA 3. (3 n2 n=2 2 (n=27 ( n= (n=2 (n= (n

More attention has been paid to immunotherapy for ovarian cancer and the development of tumor vaccines. We developed a trichostatin A (TSA)-modified tumor vaccine with potent immunomodulating activities that can inhibit the growth of ovarian cancer in rats and stimulate immune cell response in vivo. TSA-treated Nutu-19 cells inactivated by X-ray radiation were used as a tumor vaccine in rat ovarian cancer models. Prophylactic and therapeutic experiments were performed with TSA-modified tumor vaccine in rats. Flow cytometry and ELISpot assays were conducted to assess immune response. Immune cell expression in the spleen and thymus were detected by immunohistochemical staining. GM-CSF, IL-7, IL-17, LIF, LIX, KC, MCP-1, MIP-2, M-CSF, IP-10/CXCL10, MIG/CXCL9, RANTES, IL-4, IFN-γ, and VEGF expressions were detected with Milliplex Map Magnetic Bead Panel immunoassay. TSA vaccination in therapeutic and prophylactic models could effectively stimulate innate immunity and boost the adaptive humoral and cell-mediated immune responses to inhibit the growth and tumorigenesis of ovarian cancer. This vaccine stimulated the thymus into reactivating status and enhanced infiltrating lymphocytes in tumor-bearing rats. The expression of key immunoregulatory factors were upregulated in the vaccine group. The intensities of infiltrating CD4+ and CD8+ T cells and NK cells were significantly increased in the vaccine group compared to the control group (P<0.05). This protection was mainly dependent on the IFN-γ pathway and, to a much lesser extent, by the IL-4 pathway. The tumor cells only irradiated by X-ray as the control group still showed a slight immune effect, indicating that irradiated cells may also cause certain immune antigen exposure, but the efficacy was not as significant as that of the TSA-modified tumor vaccine. Our study revealed the potential application of the TSA-modified tumor vaccine as a novel tumor vaccine against tumor refractoriness and growth. These findings offer a better understanding of the immunomodulatory effects of the vaccine against latent tumorigenesis and progression. This tumor vaccine therapy may increase antigen exposure, synergistically activate the immune system, and ultimately improve remission rates. A vaccine strategy designed to induce effective tumor immune response is being considered for cancer immunotherapy. vaccines TSAmodified modified vivo TSAtreated treated Nutu19 Nutu 19 Nutu-1 Xray X ray staining GMCSF, GMCSF GM CSF, CSF GM-CSF IL7, IL7 IL 7, 7 IL-7 IL17, IL17 17, 17 IL-17 LIF LIX KC MCP1, MCP1 MCP 1, 1 MCP-1 MIP2, MIP2 MIP 2, 2 MIP-2 MCSF, MCSF M M-CSF IP10/CXCL10, IP10CXCL10 IPCXCL IP 10/CXCL10, 10 CXCL10 CXCL IP-10/CXCL10 MIGCXCL9 MIGCXCL MIG CXCL9 MIG/CXCL9 RANTES IL4, IL4 4, 4 IFNγ, IFNγ IFN γ, γ immunoassay cellmediated mediated tumorbearing bearing CD4 CD CD8 P<0.05. P005 P P<0.05 . 0 05 (P<0.05) extent IL- effect exposure progression system rates Nutu1 Nutu- IL1 IL-1 MCP- MIP- IP10 IP10/CXCL10 IP10CXCL1 10CXCL10 10/CXCL10 CXCL1 IP-10/CXCL1 MIG/CXCL P00 P<0.0 (P<0.05 IP1 IP10/CXCL1 IP10CXCL 10CXCL1 10/CXCL1 IP-10/CXCL P0 P<0. (P<0.0 IP10/CXCL 10CXCL 10/CXCL P<0 (P<0. P< (P<0 (P< (P

Accumulation of visceral adipose tissue is associated with metabolic syndrome (MS), insulin resistance, and dyslipidemia. Here we examined several morphometric and biochemical parameters linked to MS in a rodent litter size reduction model, and how a 30-day fish oil (FO) supplementation affected these parameters. On day 3 post-birth, pups were divided into groups of ten or three. On day 22, rats were split into control (C) and small litter (SL) until 60 days old. Then, after metabolic disturbance and obesity were confirmed, FO supplementation started for 30 days and the new groups were named control (C), FO supplemented (FO), obese (Ob), and obese FO supplemented (ObFO). Comparison was performed by Student t-test or 2-way ANOVA followed by Tukey post hoc test. At the end of the 60-day period, SL rats were hyperphagic, obese, hypoinsulinemic, normoglycemic, and had high visceral fat depot and high interleukin (IL)-6 plasma concentration. Obese rats at 90 days of age were fatter, hyperphagic, hyperglycemic, hypertriacylgliceromic, hipoinsulinemic, with low innate immune response. IL-6 production ex vivo was higher, but in plasma it was not different from the control group. FO supplementation brought all biochemical changes to normal values, normalized food intake, and reduced body weight and fat mass in obese rats. The innate immune response was improved but still not as efficient as in lean animals. Our results suggested that as soon MS appears, FO supplementation must be used to ameliorate the morpho- and biochemical effects caused by MS and improve the innate immune response. MS, , (MS) resistance dyslipidemia model 30day (FO postbirth, postbirth birth, birth post-birth three 22 C (C (SL 6 old Then confirmed C, FO, Ob, Ob (Ob) ObFO. ObFO . (ObFO) ttest t test 2way way 2 60day period hyperphagic hypoinsulinemic normoglycemic IL6 IL (IL)- concentration 9 fatter hyperglycemic hypertriacylgliceromic hipoinsulinemic IL- higher group values intake animals appears morpho (MS (Ob (ObFO (IL) (IL