Smartphone application-based rehabilitation in patients with chronic respiratory and cardiovascular diseases.

Rehabilitation improves symptoms, quality of life, and survival in patients with chronic respiratory or cardiovascular disease. We evaluated smartphone application-based rehabilitation programs for patients with chronic respiratory or cardiovascular diseases. This was a single-center prospective single arm study. Participants underwent smartphone application-based pulmonary or cardiac rehabilitation for 12 weeks. A total of 93 participants were recruited, and 75 visited after rehabilitation. Their median age was 67.0 (interquartile range, 60.0-70.8) years, and 60 (80.0%) were men. For patients with chronic respiratory disease (n = 41), VO2peak (median 13.7 to 15.4 ml/kg/min, P = 0.049), chronic obstructive pulmonary disease assessment test (median 14 to 6, P < 0.001), Euro-QoL 5-Dimension 5-Level (EQ-5D-5L) index (median 0.795 to 0.862, P = 0.001), and Health-related Quality of Life Instrument with 8 Items (HINT-8) index (median 0.784 to 0.855, P < 0.001) were significantly improved. For patients with chronic cardiovascular disease (n = 34), VO2peak (median 21.8 to 23.3, P = 0.007), EQ-5D-5L index (median 0.871 to 1.000, P = 0.037), and HINT-8 index (median 0.890 to 0.903, P < 0.001) were significantly improved. The smartphone application-based rehabilitation program improved exercise capacity and quality of life in patients with chronic respiratory or cardiovascular disease.Trial registration: https://clinicaltrials.gov/ct2/show/NCT05383950 (20/05/2022).

Decode-MOT: How Can We Hurdle Frames to Go Beyond Tracking-by-Detection?

The speed of tracking-by-detection (TBD) greatly depends on the number of running a detector because the detection is the most expensive operation in TBD. In many practical cases, multi-object tracking (MOT) can be, however, achieved based tracking-by-motion (TBM) only. This is a possible solution without much loss of MOT accuracy when the variations of object cardinality and motions are not much within consecutive frames. Therefore, the MOT problem can be transformed to find the best TBD and TBM mechanism. To achieve it, we propose a novel decision coordinator for MOT (Decode-MOT) which can determine the best TBD/TBM mechanism according to scene and tracking contexts. In specific, our Decode-MOT learns tracking and scene contextual similarities between frames. Because the contextual similarities can vary significantly according to the used trackers and tracking scenes, we learn the Decode-MOT via self-supervision. The evaluation results on MOT challenge datasets prove that our method can boost the tracking speed greatly while keeping the state-of-the-art MOT accuracy. Our code will be available at https://github.com/reussite-cv/Decode-MOT.

Cell-penetrating TLR inhibitor peptide alleviates ulcerative colitis by the functional modulation of macrophages.

Toll-like receptors (TLRs) have a crucial role not only in triggering innate responses against microbes but in orchestrating an appropriate adaptive immunity. However, deregulated activation of TLR signaling leads to chronic inflammatory conditions such as inflammatory bowel disease (IBD). In this study, we evaluated the immunomodulatory potential of a TLR inhibitor in the form of a cell-penetrating peptide using an ulcerative colitis animal model. A peptide derived from the TIR domain of the TLR adaptor molecule TIRAP that was conjugated with a cell-penetrating sequence (cpTLR-i) suppressed the induction of pro-inflammatory cytokines such as TNF-α and IL-1ß in macrophages. In DSS-induced colitis mice, cpTLR-i treatment ameliorated colitis symptoms, colonic tissue damage, and mucosal inflammation. Intriguingly, cpTLR-i attenuated the induction of TNF-α-expressing proinflammatory macrophages while promoting that of regulatory macrophages expressing arginase-1 and reduced type 17 helper T cell (Th17) responses in the inflamed colonic lamina propria. An in vitro study validated that cpTLR-i enhanced the differentiation of monocyte-driven macrophages into mature macrophages with a regulatory phenotype in a microbial TLR ligand-independent manner. Furthermore, the cocultivation of CD4 T cells with macrophages revealed that cpTLR-i suppressed the activation of Th17 cells through the functional modulation of macrophages. Taken together, our data show the immunomodulatory potential of the TLR inhibitor peptide and suggest cpTLR-i as a novel therapeutic candidate for the treatment of IBD.

Preventive Activity of Patchouli Alcohol Against Colorectal Cancer and Diabetes.

Patchouli alcohol (PA) is a tricyclic sesquiterpene and the dominant bioactive component in oil extracted from the aerial parts of Pogostemon cablin (patchouli). It has been reported to possess diverse health-beneficial activities, including anti-inflammatory, antiobese, and anticancer activities. However, preclinical studies are required to explore the possibility of developing PA as a promising functional and promising drug for the prevention and treatment of human diseases. In this study, we used animal models to examine whether PA shows benefits in inflammation-induced colorectal cancer and obesity-induced diabetes. ApcMin/+ mice for colorectal cancer model were treated PA 0, 25 and 50 mg/kg body weight three times a week for 6 weeks along with 2% dextran sulfate sodium (DSS) in drinking water for 1 week. High-fat diet (HFD)-induced obesity mice were treated with PA 0, 25, and 50 mg/kg bodyweight three times a week for 8 weeks. Oral administration of PA to ApcMin/+ mice treated with DSS significantly suppressed formation and development of tumors in both small and large intestines. In cell culture using Caco-2 human colorectal cancer cells, treatment of culture media with PA suppressed proliferation and induced G1-phase growth arrest. In a mouse model of HFD-induced obesity, glucose tolerance tests indicated the same orally administered dose of PA to significantly reduce blood glucose. In vitro assays in differentiated C2C12 myocytes further demonstrated PA to significantly enhance glucose uptake and increase phosphorylation of 5' adenosine monophosphate-activated protein kinase and protein kinase B. This study demonstrates that PA might possess health beneficial effects on colorectal cancer and obesity-induced diabetes.

Indole-3-Carbinol: Occurrence, Health-Beneficial Properties, and Cellular/Molecular Mechanisms.

Indole-3-carbinol (I3C) is a bioactive phytochemical abundant in cruciferous vegetables. One of its main in vivo metabolites is 3,3'-diindolylmethane (DIM), formed by the condensation of two molecules of I3C. Both I3C and DIM alter multiple signaling pathways and related molecules controlling diverse cellular events, including oxidation, inflammation, proliferation, differentiation, apoptosis, angiogenesis, and immunity. There is a growing body of evidence from both in vitro and in vivo models that these compounds possess strong potential to prevent several forms of chronic disease such as inflammation, obesity, diabetes, cardiovascular disease, cancer, hypertension, neurodegenerative diseases, and osteoporosis. This article reviews current knowledge of the occurrence of I3C in nature and foods, along with the beneficial effects of I3C and DIM concerning prevention and treatment of human chronic diseases, focusing on preclinical studies and their mechanisms of action at cellular and molecular levels.

Dynamic Shear Texture Evolution during the Symmetric and Differential Speed Rolling of Al-Si-Mg Alloys Fabricated by Twin Roll Casting.

The effects of a reduction in area (RA) and the speed ratio between the top and bottom rolls on a shear strain and the crystallographic texture evolution of Al-Si-Mg (1.0%Si-0.6%Mg) aluminum alloys fabricated by twin roll casting (TRC) were comprehensively examined experimentally and through numerical predictions. Initial twin-roll casted strips had a texture gradient from the surface to the center. ⟨111⟩//ND textures were found in the surface layer, and weak rolling textures existed in the center of the strip. The distributions of shear and plane strain compression (PSC) textures varied with the RA and differential speed ratio. Strong shear textures including a rotated cube, {100}⟨011⟩, were obtained from both the symmetric and differential speed rolling processes. Symmetric rolling with a different reduction in area (SRDRA) produced shear textures mainly in the surface layer. Differential speed rolling (DSR) caused dynamic shear textures along the thickness direction, not limited to the surface. Based on the finite element method and crystal plasticity, the effects of different RA values, differential speed ratios, and friction coefficients on shear strain and texture evolution are discussed in detail. Loads measured from work rolls during DSR decreased with an increase in the speed ratio.

Effective Multi-Object Tracking via Global Object Models and Object Constraint Learning.

Effective multi-object tracking is still challenging due to the trade-off between tracking accuracy and speed. Because the recent multi-object tracking (MOT) methods leverage object appearance and motion models so as to associate detections between consecutive frames, the key for effective multi-object tracking is to reduce the computational complexity of learning both models. To this end, this work proposes global appearance and motion models to discriminate multiple objects instead of learning local object-specific models. In concrete detail, it learns a global appearance model using contrastive learning between object appearances. In addition, we learn a global relation motion model using relative motion learning between objects. Moreover, this paper proposes object constraint learning for improving tracking efficiency. This study considers the discriminability of the models as a constraint, and learns both models when inconsistency with the constraint occurs. Therefore, object constraint learning differs from the conventional online learning for multi-object tracking which updates learnable parameters per frame. This work incorporates global models and object constraint learning into the confidence-based association method, and compare our tracker with the state-of-the-art methods on public available MOT Challenge datasets. As a result, we achieve 64.5% MOTA (multi-object tracking accuracy) and 6.54 Hz tracking speed on the MOT16 test dataset. The comparison results show that our methods can contribute to improve tracking accuracy and tracking speed together.

Effects of isoflurane anesthesia on addictive behaviors in rats.

RATIONALE: Recently, it has been suggested that isoflurane might reduce dopamine release from rat midbrain dopaminergic neurons, the neurobiological substrate implicated in the reinforcing effects of abused drugs and nondrug rewards. However, little is known about effects of isoflurane on neurobehavioral activity associated with chronic exposure to psychoactive substances. OBJECTIVE: The present study was designed to investigate the effects of isoflurane on cocaine-reinforced behavior. Using behavioral paradigm in rats, we evaluated the effects of isoflurane on cocaine self-administration under fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement. We also tested the effects of isoflurane on lever responding by nondrug reinforcers (sucrose and food) in drug-naive rats to control for the nonselective effects of isoflurane on cocaine- and nicotine-taking behavior. To further assess the ability of isoflurane to modulate the motivation for taking a drug, we evaluated the effects of isoflurane on nicotine self-administration. Using different groups of rats, the effects of isoflurane on the locomotor activity induced by a single intraperitoneal injection of cocaine (15 mg/kg) were also examined. RESULTS: Isoflurane significantly suppressed the self-administration of cocaine and nicotine without affecting food consumption. Unlike food-reinforced responding, responding for sucrose reinforcement was decreased by isoflurane. Isoflurane reduced breaking points under a PR schedule of reinforcement in a dose-dependent manner, indicating its efficacy in decreasing the incentive value of cocaine. Isoflurane also attenuated acute cocaine-induced hyperlocomotion. CONCLUSIONS: The results provided evidence that isoflurane decreases cocaine- and nicotine-reinforced responses, while isoflurane effect is not selective for cocaine- and nicotine-maintained responding. These results suggest that isoflurane inhibitions of cocaine- and nicotine-maintenance responses may be related to decreased effects of dopamine, and further investigation will need to elucidate this relationship.

Pendimethalin induces apoptotic cell death through activating ER stress-mediated mitochondrial dysfunction in human umbilical vein endothelial cells.

Pendimethalin is globally registered for control of a wide range of weeds in agriculture and home landscaping. Human exposure to pendimethalin can occur by the oral route through food and other sources. Endothelial function is vital to numerous biological processes, and endothelial dysfunction and poor vascular health is associated with increased atherosclerotic events; however, no study has yet investigated the potential effect of pendimethalin on endothelial function and vasculature formation. The objective of the current study is to investigate if pendimethalin may affect the viability and function of vascular endothelial cells. We observed that pendimethalin significantly repressed viability of human endothelial cells, inducing G1 cell cycle arrest and apoptotic/necrotic cell death. Pendimethalin treatment also activated ER stress and autophagy, leading to loss of mitochondrial membrane potential. In addition, pendimethalin impaired the tube forming and migratory abilities of endothelial cells. This study provides previously unrecognized adverse effects of pendimethalin in vascular endothelial cells, mediated by ER stress-induced mitochondrial dysfunction.

Soluble Free, Soluble Conjugated, and Insoluble Bound Phenolics in Tomato Seeds and Their Radical Scavenging and Antiproliferative Activities.

The soluble free, soluble conjugated, and insoluble bound phenolic compounds in tomato seeds were extracted and analyzed using ultra-high-performance liquid chromatography-high-resolution mass spectrometry. Total phenolic content (TPC) and free radical scavenging activities along with the antiproliferative effects against the human colorectal cancer cell line (HCT-116) were also examined for the soluble free, soluble conjugated, and insoluble bound phenolic fractions. 13, 7, and 10 compounds were tentatively identified in the soluble free, soluble conjugated, and insoluble bound phenolic fractions, respectively, including indole-3-acetic acid derivatives, flavonoids, phenolic acid, and tyramine-derived hydroxycinnamic acid amines. The insoluble bound phenolic fraction was observed to have a greater TPC value and stronger free radical scavenging activities against ABTS•+, DPPH•, and peroxyl radicals and a stronger inhibitory effect against HCT-116 cells compared with the soluble free and the soluble conjugated fractions. Soluble free and insoluble bound fractions significantly inhibited the proliferation of the HCT-116 cell line, and no antiproliferative effects were observed with the soluble conjugated fraction under the experimental conditions. The results may provide a foundation for future application of tomato seeds as nutraceuticals in dietary supplements and functional foods.

Prediction of the composition of urinary stones using deep learning.

PURPOSE: This study aimed to predict the composition of urolithiasis using deep learning from urinary stone images. MATERIALS AND METHODS: We classified 1,332 stones into 31 classes according to the stone composition. The top 4 classes with a frequency of 110 or more (class 1: calcium oxalate monohydrate [COM] 100%, class 2: COM 80%+struvite 20%, class 3: COM 60%+calcium oxalate dihydrate [COD] 40%, class 4: uric acid 100%) were selected. With the 965 stone images of the top 4 classes, we used the seven convolutional neural networks (CNN) to classify urinary stones and compared their classification performances. RESULTS: Among the seven models, Xception_Ir0.001 showed the highest accuracy, precision, and recall and was selected as the CNN model to predict the stone composition. The sensitivity and specificity for the 4 classes by Xception_Ir0.001 were as follows: class 1 (94.24%, 91.73%), class 2 (85.42%, 96.14%), class 3 (86.86%, 99.59%), and class 4 (94.96%, 98.82%). The sensitivity and specificity of the individual components of the stones were as follows. COM (98.82%, 94.96%), COD (86.86%, 99.64%), struvite (85.42%, 95.59%), and uric acid (94.96%, 98.82%). The area under the curves for class 1, 2, 3, and 4 were 0.98, 0.97, 1.00, and 1.00, respectively. CONCLUSIONS: This study showed the feasibility of deep learning for the diagnostic ability to assess urinary stone composition from images. It can be an alternative tool for conventional stone analysis and provide decision support to urologists, improving the effectiveness of diagnosis and treatment.

Correlation Comparison and Personalized Utility of Field Walking Tests in Assessing the Exercise Capacity of Patients with Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial.

Background: Incremental shuttle walking tests (ISWT) are regarded as valuable alternatives to 6-min walking tests (6MWT) and cardiopulmonary exercise tests (CPET) owing to the maximal and externally paced loading. This study investigated the validity and reliability of ISWT by analyzing the correlation of the distances of two field tests with peak oxygen consumption (VO2) of CPET in patients with COPD. Methods: In this randomized controlled trial, patients with COPD were enrolled from two hospitals. Three assessments were performed for all patients. The ISWT and 6MWT were repeated twice in Hospital 1 to assess reliability. Results: A total of 29 patients were enrolled. The distances of ISWT (0.782, p < 0.001) and 6MWT (0.512, p = 0.005) correlated with peak VO2. The intraclass correlation coefficients of both ISWT (0.988, p < 0.001) and 6MWT (0.959, p < 0.001) was high. Patients with higher peak VO2 walked a longer distance in ISWT than 6MWT (r = 0.590, p < 0.001). Conclusions: The ISWT more highly correlates with peak VO2 than the 6MWT and has excellent reliability in patients with COPD. According to peak VO2, the walking distances of each field test varied, suggesting that the application should be personalized for the exercise capacity.

Cannabidiol exerts anti-proliferative activity via a cannabinoid receptor 2-dependent mechanism in human colorectal cancer cells.

Colorectal cancer is the third leading cause of cancer incidence and mortality in the United States. Cannabidiol (CBD), the second most abundant phytocannabinoid in Cannabis sativa, has potential use in cancer treatment on the basis of many studies showing its anti-cancer activity in diverse types of cancer, including colon cancer. However, its mechanism of action is not yet fully understood. In the current study, we observed CBD to repress viability of different human colorectal cancer cells in a dose-dependent manner. CBD treatment led to G1-phase cell cycle arrest and an increased sub-G1 population (apoptotic cells); it also downregulated protein expression of cyclin D1, cyclin D3, cyclin-dependent kinase 2 (CDK2), CDK4, and CDK6. CBD further increased caspase 3/7 activity and cleaved poly(ADP-ribose) polymerase, and elevated expression of endoplasmic reticulum (ER) stress proteins including binding immunoglobulin protein (BiP), inositol-requiring enzyme 1α (IRE1α), phosphorylated eukaryotic initiation factor 2α (eIF2α), activating transcription factor 3 (ATF3), and ATF4. We found that CBD repressed cell viability and induced apoptotic cell death through a mechanism dependent on cannabinoid receptor type 2 (CB2), but not on CB1, transient receptor potential vanilloid, or peroxisome proliferator-activated receptor gamma. Anti-proliferative activity was also observed for other non-psychoactive cannabinoid derivatives including cannabidivarin (CBDV), cannabigerol (CBG), cannabicyclol (CBL), and cannabigerovarin (CBGV). Our data indicate that CBD and its derivatives could be promising agents for the prevention of human colorectal cancer.

Anti-Adipogenic Activity of High-Phenolic Sorghum Brans in Pre-Adipocytes.

Obesity is one of the leading public health problems that can result in life-threatening metabolic and chronic diseases such as cardiovascular diseases, diabetes, and cancer. Sorghum (Sorghum bicolor (L.) Moench) is the fifth most important cereal crop in the world and certain genotypes of sorghum have high polyphenol content. PI570481, SC84, and commercially available sumac sorghum are high-polyphenol genotypes that have demonstrated strong anti-cancer activities in previous studies. The objective of this study was to explore a potential anti-obesity use of extracts from sorghum bran in the differentiation of 3T3-L1 preadipocytes and to investigate cellular and molecular responses in differentiated adipocytes to elucidate related mechanisms. None of the four different sorghum bran extracts (PI570481, SC84, Sumac, and white sorghum as a low-polyphenol control) caused cytotoxicity in undifferentiated and differentiated 3T3-L1 cells at doses used in this study. Sorghum bran extracts (PI570481, SC84, and Sumac) reduced intracellular lipid accumulation and expression of adipogenic and lipogenic proteins in a dose-dependent manner in differentiated 3T3-L1 cells. The same polyphenol containing sorghum bran extracts also repressed production of reactive oxygen species (ROS) and MAPK signaling pathways and repressed insulin signaling and glucose uptake in differentiated 3T3-L1 cells. These data propose a potential use of high-phenolic sorghum bran for the prevention of obesity.

Protocatechuic acid protects hepatocytes against hydrogen peroxide-induced oxidative stress.

Oxidative stress is a main cause of tissue damage and highly associated with incidence of human chronic diseases. Among the major target organs attacked by reactive oxygen species (ROS) is the liver. Protocatechuic acid (PCA) is a phenolic compound found in green tea, acai oil and some mushroom species that possesses strong antioxidative and anti-inflammatory activity and may have benefits as a natural phytochemical for prevention of human diseases. However, the protective effect of PCA on hydrogen peroxide (H2O2)-induced oxidative stress specifically in the liver has not yet been investigated. The current study aims to observe if PCA possesses protective activity against H2O2-induced oxidative stress in HepG2 human liver cancer cells. Relative to untreated control cells, treatment of HepG2 cells with PCA reduced H2O2-induced cell death and mitigated H2O2-induced production of ROS; furthermore, it mitigated the H2O2-induced increase of caspase-3/7 enzyme activity, expression of cleaved poly(ADP-ribose) polymerase (PARP), expression of endoplasmic reticulum (ER) stress genes including activating transcription factor 4 (ATF4), serine/threonine-protein kinase/endoribonuclease inositol-requiring enzyme 1 α (IRE1α) and phosphorylation of p38 mitogen-activated protein kinases (MAPK). These findings indicate that PCA effectively protects hepatic cells from H2O2-induced oxidative stress and cell death.

Permethrin inhibits tube formation and viability of endothelial cells.

BACKGROUND: Exposure to environmental chemicals has been linked with endothelial dysfunction, which is a leading cause of human diseases, including atherosclerosis. Permethrin is a frequently used synthetic pyrethroid insecticide for which longer exposure may cause toxicity in several types of tissues and the development of metabolic diseases, including atherosclerosis, obesity and diabetes. The present study was designed to evaluate the potential adverse effect of permethrin on the function and activity of human endothelial cells. RESULTS: Permethrin was found to repress migration and tube formation by human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner, as well as to significantly repress their viability after 24 and 48 h of treatment. Furthermore, increased reactive oxygen species (ROS) production was observed in cells treated with permethrin, and the permethrin-induced repression of cell viability was ROS-dependent. Permethrin did not influence apoptosis, necrosis or mitochondrial membrane potential in HUVECs. CONCLUSION: The results of the present study suggest that permethrin represses angiogenesis and viability through ROS-dependent and cell growth-, apoptosis- and necrosis-independent means. © 2022 Society of Chemical Industry.

Silodosin for Prevention of Ureteral Injuries Resulting from Insertion of a Ureteral Access Sheath: A Randomized Controlled Trial.

BACKGROUND: The ureteral access sheath (UAS) is an ancillary device widely used by urologists, but acute ureter injury may occur following its insertion. Preoperative selective oral α1-blockers can reduce intraureteral pressure, and prevent ureteral wall injury during UAS insertion. OBJECTIVE: To compare perioperative data of patients who underwent flexible ureterorenoscopy (fURS) with UAS with and without premedication with silodosin. DESIGN, SETTING, AND PARTICIPANTS: Single-blind, 100 patients from a single institution who underwent retrograde intrarenal surgery for kidney and upper ureter stone removal were prospectively allocated from May 2018 to March 2019. INTERVENTION: The experimental groups received silodosin for 3 d preoperatively. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint included ureteral injuries after UAS insertion that were assessed according to endoscopic classification. The secondary endpoint was an evaluation of whether premedication with silodosin had any effect on postoperative outcomes. RESULTS AND LIMITATIONS: A total of 44 and 43 patients were randomly assigned to the control and experimental groups, respectively. Silodosin prevented significant postoperative ureteral injury involving the smooth muscle layer more successfully than in the control group (9.3% vs 27.3%; p = 0.031). There was no significant difference in the overall complication rate as determined by the modified Clavien-Dindo classification system and the computed tomography scan stone-free rate postoperatively. Patients who received silodosin before fURS reported lower pain scores than those in the control group using a visual analog scale (p = 0.009). Limitation included a lack of placebo comparison. CONCLUSIONS: Our data suggest that preoperative silodosin protects against significant ureteral injury related to UAS insertion during fURS and decreases postoperative pain level. Silodosin premedication might be an effective and safe technique to replace prestenting. PATIENT SUMMARY: We investigated the preventive effect of an α-blocker against perioperative complication caused by ureteral access sheath inserted during flexible ureterorenoscopy. Taking silodosin before surgery prevented ureter wall injury during surgery and immediately improved postoperative pain.

RNA-Seq Reveals Different Gene Expression in Liver-Specific Prohibitin 1 Knock-Out Mice.

Prohibitin 1 (PHB1) is an evolutionarily conserved and ubiquitously expressed protein that stabilizes mitochondrial chaperone. Our previous studies showed that liver-specific Phb1 deficiency induced liver injuries and aggravated lipopolysaccharide (LPS)-induced innate immune responses. In this study, we performed RNA-sequencing (RNA-seq) analysis with liver tissues to investigate global gene expression among liver-specific Phb1-/-, Phb1+/-, and WT mice, focusing on the differentially expressed (DE) genes between Phb1+/- and WT. When 78 DE genes were analyzed for biological functions, using ingenuity pathway analysis (IPA) tool, lipid metabolism-related genes, including insulin receptor (Insr), sterol regulatory element-binding transcription factor 1 (Srebf1), Srebf2, and SREBP cleavage-activating protein (Scap) appeared to be downregulated in liver-specific Phb1+/- compared with WT. Diseases and biofunctions analyses conducted by IPA verified that hepatic system diseases, including liver fibrosis, liver hyperplasia/hyperproliferation, and liver necrosis/cell death, which may be caused by hepatotoxicity, were highly associated with liver-specific Phb1 deficiency in mice. Interestingly, of liver disease-related 5 DE genes between Phb1+/- and WT, the mRNA expressions of forkhead box M1 (Foxm1) and TIMP inhibitor of metalloproteinase (Timp1) were matched with validation for RNA-seq in liver tissues and AML12 cells transfected with Phb1 siRNA. The results in this study provide additional insights into molecular mechanisms responsible for increasing susceptibility of liver injuries associated with hepatic Phb1.

Nanocomplex-Mediated In Vivo Programming to Chimeric Antigen Receptor-M1 Macrophages for Cancer Therapy.

Chimeric antigen receptor-T (CAR-T) cell immunotherapy has shown impressive clinical outcomes for hematologic malignancies. However, its broader applications are challenged due to its complex ex vivo cell-manufacturing procedures and low therapeutic efficacy against solid tumors. The limited therapeutic effects are partially due to limited CAR-T cell infiltration to solid tumors and inactivation of CAR-T cells by the immunosuppressive tumor microenvironment. Here, a facile approach is presented to in vivo program macrophages, which can intrinsically penetrate solid tumors, into CAR-M1 macrophages displaying enhanced cancer-directed phagocytosis and anti-tumor activity. In vivo injected nanocomplexes of macrophage-targeting nanocarriers and CAR-interferon-γ-encoding plasmid DNA induce CAR-M1 macrophages that are capable of CAR-mediated cancer phagocytosis, anti-tumor immunomodulation, and inhibition of solid tumor growth. Together, this study describes an off-the-shelf CAR-macrophage therapy that is effective for solid tumors and avoids the complex and costly processes of ex vivo CAR-cell manufacturing.

Polyphenol Containing Sorghum Brans Exhibit an Anti-Cancer Effect in Apc Min/+ Mice Treated with Dextran Sodium Sulfate.

Colon cancer (CC) is considered a high-risk cancer in developed countries. Its etiology is correlated with a high consumption of red meat and low consumption of plant-based foods, including whole grains. Sorghum bran is rich in polyphenols. This study aimed to determine whether different high-phenolic sorghum brans suppress tumor formation in a genetic CC rodent model and elucidate mechanisms. Tissue culture experiments used colorectal cancer cell lines SW480, HCT-116 and Caco-2 and measured protein expression, and protein activity. The animal model used in this study was APC Min+/mouse model combined with dextram sodium sulfate. High phenolic sorghum bran extract treatment resulted in the inhibition of proliferation and induced apoptosis in CC cell lines. Treatment with high phenolic sorghum bran extracts repressed TNF-α-stimulated NF-κB transactivation and IGF-1-stimulated PI3K/AKT pathway via the downregulation of ß-catenin transactivation. Furthermore, high-phenolic sorghum bran extracts activated AMPK and autophagy. Feeding with high-phenolic sorghum bran for 6 weeks significantly suppressed tumor formation in an APC Min/+ dextran sodium sulfate promoted CC mouse model. Our data demonstrates the potential application of high-phenolic sorghum bran as a functional food for the prevention of CC.