Konjac glucomannan-fibrin composite hydrogel as a model for ideal scaffolds for cell-culture meat.

In this study, composite gel was prepared from konjac glucomannan (KGM) and fibrin (FN). Composite gels with different concentration ratios were compared in terms of their mechanical properties, rheological properties, water retention, degradation rate, microstructure and biocompatibility. The results showed that the composite gels had better gel strength and other properties than non-composite gels. In particular, composite hydrogels with low Young's modulus formed when the KGM concentration was 0.8% and the FN concentration was 1.2%. The two components were cross linked through hydrogen-bond interaction, which formed a more stable gel structure with excellent water retention and in-vitro degradation rates, which were conducive to myogenic differentiation of ectomesenchymal stem cells (EMSCs). KGM-FN composite gel was applied to the preparation of cell-culture meat, which had similar texture properties and main nutrients to animal meat as well as higher content of dry base protein and dry base carbohydrate.

Diagnostic significance of cerebrospinal fluid flow cytometry in Chinese children with B lineage acute lymphoblastic leukemia.

BACKGROUND: Central nervous system leukemia (CNSL) is one of the major causes of the poor prognosis of childhood leukemia. We aimed to compare the sensitivity of cytomorphology (CM) and flow cytometry (FCM) in diagnosing CNSL, emphasizing the importance of FCM in the diagnosis process. METHODS: One-hundred-sixty-five children with newly diagnosed B-cell Acute Lymphoblastic Leukemia (B-cell ALL) were included in this study. Cerebrospinal fluid (CSF) samples were taken for routine CSF analysis, CM analysis, and FCM examination. Computed tomography scans and/or magnetic resonance imaging were performed at diagnosis. Patients with CNS2, CNS3, and traumatic lumbar puncture (TLP) at diagnosis received two additional courses of triple intrathecal injections during induction treatment. We compared the sensitivity of FCM and CM in the diagnosis of children with CNSL. RESULTS: One hundred and twenty-eight (77.58%) CSF samples were negative by either CM or FCM (CM-/FCM-), four (2.42%) were positive by both CM and FCM (CM+/FCM+), and thirty-three (20%) displayed a single positive finding by FCM (CM-/FCM+) (p = 0.044). By adding two intrathecal injections in the induction treatment, ten children with TLP+ had no CNS relapse, like those with TLP-. However, compared to CNS1 and TLP, the event-free survival (EFS) did not significantly improve in patients with CNS2 and CNS3. Moreover, CNSL status was associated with worse 3-year EFS (p < 0.05). CONCLUSIONS: We have validated that FCM is more accurate in stratifying the status of the CNS compared to CM analysis. However, to improve the EFS rate of childhood leukemia, it is necessary to combine CM examination, FCM, and cranial imaging for the early diagnosis of CNSL.

Rare flavanone-diarylheptanoid hybrids from Typha angustifolia shows anti breast cancer activity via activating TGF-ß1/Smad signaling pathway.

Four new flavanone-diarylheptanoid hetero dimers, typhatifolins A-D (1-4), were separated from the pollen of a widely distributed medicinal plant Typha angustifolia. Structures of these rare hybrids were elucidated by detailed interpretation of spectroscopic data, and their absolute configurations were determined on the basis of Mosher's method and ECD analyses. All the four compounds showed moderate to significant cytotoxicities against a panel of tumor cell lines with IC50 values ranging from 0.67 to 12.48 µM. Further in vitro antitumor evaluation for typhatifolin B (TTB, 2) on two breast cancer cells (4T1 and MDA-MB231) revealed that it could remarkably induce cell apoptosis and G0/G1 cycle arrest, as well as block cell migration and invasion. Mechanistically, TTB could exert its antitumor effect via activating the TGF-ß1 (transforming growth factor beta 1) signaling pathway as evidenced by RNA-seq analysis and immunoblotting experiments, which was further corroborated by treating cancer cells with a TGF-ß signaling inhibitor. Lastly, the in vivo anti breast cancer activity was demonstrated by applying the mixture of typhatifolins A-D to a preclinical animal model.

Clinical benefit analysis of PD-1 inhibitors in patients with advanced, recurrent or metastatic cervical cancer: a meta-analysis and systematic review.

Purpose: This study aims to comprehensively evaluate the efficacy and safety of programmed cell death protein-1 (PD-1) in patients with advanced, recurrent, or metastatic cervical cancer (ARMCC) and identify the population that may benefit the most. Methods: We conducted a search of PubMed, EMBASE, and the Cochrane Collaboration Library from their inception to September 2023. We extracted and analyzed the results related to the efficacy and safety of PD-1 in patients with ARMCC. The primary endpoints included the overall objective response rate (ORR) and adverse events (AEs), while the secondary endpoints encompassed the 1-year overall survival (OS) rate, 1-year progression-free survival (PFS) rate, as well as OS and PFS. We used a random effects model to conduct a meta-analysis on single-group rates, and the Mantel-Haenszel method was utilized to compare the ORR and the incidence of AEs. Results: Our study included a total of 21 trials involving 2,097 patients. The ORR of the combination of PD-1 inhibitors with chemotherapy was 56.36%, the combination of PD-1 inhibitors with anti-angiogenic agents was 38.72%, the combination of PD-1 inhibitors with Cytotoxic T-lymphocyte antigen 4 inhibitors was 25.60%, and PD-1 inhibitor monotherapy was 15.99%. The subgroup analysis showed that the group of patients with squamous cell carcinoma (SCC) exhibited a significantly higher ORR compared to the non-SCC group in patients who received PD-1 inhibitors combined with other anti-tumor drugs (Odds Ratio =2.43, P=0.002). Additionally, the group of patients with a programmed death-ligand 1 combined positive score (PD-L1 CPS) ≥1 exhibited a significantly higher ORR compared to the PD-L1 CPS <1 group in patients who received PD-1 inhibitor monotherapy (OR=4.14, P=0.02). PD-1 inhibitor monotherapy or PD-1 inhibitors combined with chemotherapy did not significantly increase the incidence of all grades of adverse events (Relative Risk=0.99, p=0.788) or the incidence of serious adverse events (RR=0.99, p=0.788) compared to chemotherapy alone. Conclusion: PD-1 inhibitors demonstrate outstanding efficacy in the treatment of patients with ARMCC. Patients with SCC may benefit more from treatments including PD-1 inhibitors in combination with other anti-tumor drugs, and PD-L1 CPS ≥1 can be considered a favorable indicator of immune therapy response. Importantly, the use of PD-1 inhibitor monotherapy or PD-1 inhibitors in combination with chemotherapy did not lead to an increased incidence of AEs compared with chemotherapy alone, indicting safety during treatment. Systematic Review Registration: PROSPERO (CRD42023457945).

CT-Based Super-Resolution Deep Learning Models with Attention Mechanisms for Predicting Spread Through Air Spaces of Solid or Part-Solid Lung Adenocarcinoma.

RATIONALE AND OBJECTIVES: Spread through air space (STAS) is a novel invasive pattern of lung adenocarcinoma (LUAD), and preoperative knowledge of STAS status is helpful in choosing an appropriate surgical approach. MATERIALS AND METHODS: This retrospective study collected and analyzed 602 patients diagnosed with LUAD from two medical centers: center 1 was randomly partitioned into training (n = 358) and validation cohorts (n = 154) at a 7:3 ratio; and center 2 was the external test cohort (n = 90). Super resolution was performed on all images to acquire high-resolution images, which were used to train the SE-ResNet50 model, before creating an equivalent parameter ResNet50 model. Disparities were compared between the two models using receiver operating characteristic curves, area under the curve, accuracy, precision, sensitivity, and specificity. RESULTS: In this study, 512 and 90 patients with LUAD were enrolled from centers 1 and 2, respectively. The curve values of the SE-ResNet50 and ResNet50 models were compared for training, validation, and test cohorts, resulting in values of 0.933 vs 0.909, 0.783 vs 0.728, and 0.806 vs 0.695, respectively. In the external test cohort, the accuracy of the SE-ResNet50 model demonstrated a 10% improvement over the ResNet50 model (82.2% vs 72.2%). CONCLUSION: The SE-ResNet50 model based on computed tomography super-resolution has great potential for predicting STAS status in patients with solid or partially solid LUAD, with superior predictive performance compared to traditional deep learning models.

Preventive effects of caffeine on nicotine plus high-fat diet-induced hepatic steatosis and gain weight: a possible explanation for why obese smokers with high coffee consumption tend to be leaner.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver disorder, affecting approximately 25 % of the population. Coffee-drinking obese smokers exhibit lower body weights and decreased NAFLD rates, but the reasons behind this remain unclear. Additionally, the effect of nicotine, the main component of tobacco, on the development of NAFLD is still controversial. Our study aimed to explore the possible reasons that drinking coffee could alleviate NAFLD and gain weight and identify the real role of nicotine in NAFLD of obese smokers. A NAFLD model in mice was induced by administering nicotine and a high-fat diet (HFD). We recorded changes in body weight and daily food intake, measured the weights of the liver and visceral fat, and observed liver and adipose tissue histopathology. Lipid levels, liver function, liver malondialdehyde (MDA), superoxide dismutase (SOD), serum inflammatory cytokine levels and the expression of hepatic genes involved in lipid metabolism were determined. Our results demonstrated that nicotine exacerbated the development of NAFLD and caffeine had a hepatoprotective effect on NAFLD. The administration of caffeine could ameliorate nicotine-plus-HFD-induced NAFLD by reducing lipid accumulation, regulating hepatic lipid metabolism, alleviating oxidative stress, attenuating inflammatory response and restoring hepatic functions. These results might explain why obese smokers with high coffee consumption exhibit the lower incidence rate of NAFLD and tend to be leaner. It is essential to emphasise that the detrimental impact of smoking on health is multifaceted. Smoking cessation remains the sole practical and effective strategy for averting the tobacco-related complications and reducing the risk of mortality.

Rare synchronous colorectal carcinoma with three pathological subtypes: A case report and review of the literature.

BACKGROUND: Synchronous colorectal carcinomas (SCRC) are two or more primary colorectal carcinomas identified simultaneously or within 6 mo of the initial presentation in a single patient. Their incidence is low and the number of pathological types of SCRC is usually no more than two. It is very unusual that the pathological findings of a patient with SCRC show more than two different pathological subtypes. Here, we report a rare case of SCRC with three pathological subtypes. CASE SUMMARY: A 75-year-old woman who had no previous medical history or family history was admitted to the hospital because of intermittent hematochezia for more than a month. Colonoscopy displayed an irregularly shaped neoplasm of the rectum, a tumor-like lesion causing intestinal stenosis in the descending colon, and a polypoidal neoplasm in the ileocecum. Subsequently, she underwent total colectomy, abdominoperineal resection for rectal cancer, and ileostomy. After operation, the pathological report showed three pathological subtypes including well-differentiated adenocarcinoma of the ascending colon, moderately differentiated adenocarcinoma of the descending colon, and mucinous adenocarcinoma of the rectum. She is now recovering well and continues to be closely monitored during follow-up. CONCLUSION: Preoperative colonoscopy examination, imaging examination, and extensive intraoperative exploration play important roles in reducing the number of missed lesions.

[Blinatumomab as bridging therapy in two children with B-cell acute lymphoblastic leukemia complicated by invasive fungal disease]. / 2例急性Bæ·‹å·´ç»†èƒžç™½è¡€ç— åˆå¹¶ä¾µè¢­æ€§çœŸèŒç— å„¿ç«¥åº”ç”¨è´æž—å¦¥æ¬§å•æŠ—æ¡¥æŽ¥æ²»ç–—åˆ†æž.

This article reports two cases of children with B-cell acute lymphoblastic leukemia (B-ALL) complicated by invasive fungal disease (IFD) who received bridging treatment using blinatumomab. Case 1 was a 4-month-old female infant who experienced recurrent high fever and limb weakness during chemotherapy. Blood culture was negative, and next-generation sequencing (NGS) of peripheral blood, bronchoalveolar lavage fluid, and cerebrospinal fluid were all negative. Chest CT and cranial MRI revealed obvious infection foci. Case 2 was a 2-year-old male patient who experienced recurrent high fever with multiple inflammatory masses during chemotherapy. Candida tropicalis was detected in peripheral blood and abscess fluid using NGS, while blood culture and imaging examinations showed no obvious abnormalities. After antifungal and blinatumomab therapy, both cases showed significant improvement in symptoms, signs, and imaging, and B-ALL remained in continuous remission. The report indicates that bridging treatment with blinatumomab in children with B-ALL complicated by IFD can rebuild the immune system and control the underlying disease in the presence of immunosuppression and severe fungal infection.

Habitat-based radiomics enhances the ability to predict lymphovascular space invasion in cervical cancer: a multi-center study.

Introduction: Lymphovascular space invasion (LVSI) is associated with lymph node metastasis and poor prognosis in cervical cancer. In this study, we investigated the potential of radiomics, derived from magnetic resonance (MR) images using habitat analysis, as a non-invasive surrogate biomarker for predicting LVSI in cervical cancer. Methods: This retrospective study included 300 patients with cervical cancer who underwent surgical treatment at two centres (centre 1 = 198 and centre 2 = 102). Using the k-means clustering method, contrast-enhanced T1-weighted imaging (CE-T1WI) images were segmented based on voxel and entropy values, creating sub-regions within the volume ofinterest. Radiomics features were extracted from these sub-regions. Pearson correlation coefficient and least absolute shrinkage and selection operator LASSO) regression methods were used to select features associated with LVSI in cervical cancer. Support vector machine (SVM) model was developed based on the radiomics features extracted from each sub-region in the training cohort. Results: The voxels and entropy values of the CE-T1WI images were clustered into three sub-regions. In the training cohort, the AUCs of the SVM models based on radiomics features derived from the whole tumour, habitat 1, habitat 2, and habitat 3 models were 0.805 (95% confidence interval [CI]: 0.745-0.864), 0.873(95% CI: 0.824-0.922), 0.869 (95% CI: 0.821-0.917), and 0.870 (95% CI: 0.821-0.920), respectively. Compared with whole tumour model, the predictive performances of habitat 3 model was the highest in the external test cohort (0.780 [95% CI: 0.692-0.869]). Conclusions: The radiomics model based on the tumour sub-regional habitat demonstrated superior predictive performance for an LVSI in cervical cancer than that of radiomics model derived from the whole tumour.

Genome-Wide Association Analysis of Protein-Coding Variants in IgA Nephropathy.

SIGNIFICANCE STATEMENT: Genome-wide association studies have identified nearly 20 IgA nephropathy susceptibility loci. However, most nonsynonymous coding variants, particularly ones that occur rarely or at a low frequency, have not been well investigated. The authors performed a chip-based association study of IgA nephropathy in 8529 patients with the disorder and 23,224 controls. They identified a rare variant in the gene encoding vascular endothelial growth factor A (VEGFA) that was significantly associated with a two-fold increased risk of IgA nephropathy, which was further confirmed by sequencing analysis. They also identified a novel common variant in PKD1L3 that was significantly associated with lower haptoglobin protein levels. This study, which was well-powered to detect low-frequency variants with moderate to large effect sizes, helps expand our understanding of the genetic basis of IgA nephropathy susceptibility. BACKGROUND: Genome-wide association studies have identified nearly 20 susceptibility loci for IgA nephropathy. However, most nonsynonymous coding variants, particularly those occurring rarely or at a low frequency, have not been well investigated. METHODS: We performed a three-stage exome chip-based association study of coding variants in 8529 patients with IgA nephropathy and 23,224 controls, all of Han Chinese ancestry. Sequencing analysis was conducted to investigate rare coding variants that were not covered by the exome chip. We used molecular dynamic simulation to characterize the effects of mutations of VEGFA on the protein's structure and function. We also explored the relationship between the identified variants and the risk of disease progression. RESULTS: We discovered a novel rare nonsynonymous risk variant in VEGFA (odds ratio, 1.97; 95% confidence interval [95% CI], 1.61 to 2.41; P = 3.61×10 -11 ). Further sequencing of VEGFA revealed twice as many carriers of other rare variants in 2148 cases compared with 2732 controls. We also identified a common nonsynonymous risk variant in PKD1L3 (odds ratio, 1.16; 95% CI, 1.11 to 1.21; P = 1.43×10 -11 ), which was associated with lower haptoglobin protein levels. The rare VEGFA mutation could cause a conformational change and increase the binding affinity of VEGFA to its receptors. Furthermore, this variant was associated with the increased risk of kidney disease progression in IgA nephropathy (hazard ratio, 2.99; 95% CI, 1.09 to 8.21; P = 0.03). CONCLUSIONS: Our study identified two novel risk variants for IgA nephropathy in VEGFA and PKD1L3 and helps expand our understanding of the genetic basis of IgA nephropathy susceptibility.

In vitro antioxidative activity of Fritillaria cirrhosa D. Don straw ethanolic extract and its effect on lipid, protein oxidation, and quality of Chinese-style sausage.

Fritillaria cirrhosa D. Don, which can be used for medicine and food, contains a variety of chemicals including polyphenols, alkaloids, terpenoid, and others that have beneficial biological properties like antihypertension, bacteriostasis, and anti-inflammatory. The ethanolic extract of Fritillaria straw was obtained for this study using ultrasonic-aided extraction, and the amounts of total phenols and total flavonoids were 26.56 ± 1.36 mg GAE/g dw and 18.75 ± 0.80 mg RE/g dw, respectively. Ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry technology was utilized to identify 50 major chemicals in the Fritillaria straw extract (FSE). Meanwhile, the antioxidative activities of FSE were evaluated by 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and Ferric reducing antioxidant power assays in vitro, which pointed out the antioxidative potential of FSE. Additionally, 0.1%, 0.5%, and 1% of FSE and 0.02% butylated hydroxyanisole (BHA) + butylated hydroxytoluene (BHT) (1:1) were separately added to Chinese-style sausage to study their effects on the lipid oxidation, protein oxidation, and quality of the sausage at different storage times. The study found that the effect of adding 1% FSE on carbonyl content, total volatile basic nitrogen, and TVC of sausage could achieve the effect of the 0.02% BHA + BHT (1:1) group on the 35th day, and the thiobarbituric acid reactive substances value and peroxide value of sausage were significantly lower than the control group. Therefore, as one of the candidates to replace synthetic antioxidants, the FSE can be used in the production of Chinese sausages, which has a positive effect on improving the product's quality and extending the shelf life. PRACTICAL APPLICATION: The antioxidative activities of 50 main compounds were identified after the ethanolic extraction of Fritillaria straw. This Fritillaria straw extract was added to Chinese sausage, effectively inhibiting the oxidation of lipids and proteins as well as the decomposition of proteins. Obviously, the Fritillaria straw extract, one of the choices to replace synthetic antioxidants, may be useful for future meat processing, because of its positive impact on the product's quality and shelf life.

Adipocyte-Derived Extracellular Vesicles: Small Vesicles with Big Impact.

While increasing numbers of studies have established that adipose tissue plays a vital role in balancing energy intake and energy expenditure as both an energy and an endocrine organ, the detailed functions of adipose tissue remain unclear. Adipose tissues are complex, with multiple resident cell populations that communicate to diverse cells and organs via local and systemic metabolic, thermal, and inflammatory signaling. In normal physiology, adipose tissue-derived extracellular vesicles mediate the regulation of energy storage/consumption in adipose tissue, liver, and muscle. In a pathological sense, fat-derived extracellular vesicles can promote the progression of obesity, endocrine diseases, cancer, and reproductive system disorders. In this review, we demonstrate that adipocyte-derived extracellular vesicles function not only in physiological balance but also in the pathological process. We aim to illustrate the impact of adipocyte-derived extracellular vesicles and their value in understanding both homeostasis and disorders.

Long noncoding RNA XLOC_006786 inhibits the proliferation, invasion and metastasis of osteosarcoma cells through NOTCH3 signaling pathway by targeting miR-491-5p.

Recent research has indicated that Long noncoding RNAs (LncRNAs) are crucial in many disorders, especially tumors. However, the exact role of LncRNA XLOC_006786 (LncRNA-SPIDR-2:1) in malignancies, especially in human osteosarcoma, is unclear. The results of RT‒qPCR, western blotting, CCK-8 assays, and Transwell assays showed that LncRNA XLOC_006786 inhibited osteosarcoma cell proliferation, invasion, and migration, indicating that it may be a tumor suppressor gene in osteosarcoma. We found that LncRNA XLOC_006786 negatively regulated NOTCH3, which is an oncogenic gene in osteosarcoma, as we previously reported. Bioinformatics analysis showed that miR-491-5p may be a direct target of LncRNA XLOC_006786, while NOTCH3 is a key target of miR-491-5p. Then, we verified that LncRNA XLOC_006786 could prevent lung metastatic osteosarcoma in vivo. Taken together, our research showed that LncRNA XLOC_006786 suppresses osteosarcoma proliferation, invasion, and metastasis through the NOTCH3 signaling pathway by targeting miR-491-5p.

Total alkaloids of Fritillaria unibracteata var. wabuensis bulbus ameliorate chronic asthma via the TRPV1/Ca2+/NFAT pathway.

BACKGROUND: Asthma is a chronic inflammatory disease that is challenging to treat. Fritillaria unibracteata var. wabuensis (FUW) is the plant origin for the famous Chinese antitussive medicine Fritillaria Cirrhosae Bulbus. The total alkaloids of Fritillaria unibracteata var. wabuensis bulbus (TAs-FUW) have anti-inflammatory properties and may be used to treat asthma. PURPOSE: To explore whether TAs-FUW have bioactivity against airway inflammation and a therapeutic effect on chronic asthma. METHODS: The alkaloids were extracted via ultrasonication in a cryogenic chloroform-methanol solution after ammonium-hydroxide percolation of the bulbus. UPLC-Q-TOF/MS was used to characterize the composition of TAs-FUW. An ovalbumin (OVA)-induced asthmatic mouse model was established. We used whole-body plethysmography, ELISA, western blotting, RT-qPCR, and histological analyses to assess the pulmonary pathological changes in these mice after TAs-FUW treatment. Additionally, TNF-α/IL-4-induced inflammation in BEAS-2B cells was used as an in vitro model, whereby the effects of various doses of TAs-FUW on the TRPV1/Ca2+-dependent NFAT-induced expression of TSLP were assessed. Stimulation and inhibition of TRPV1 receptors by capsaicin (CAP) and capsazepine (CPZ), respectively, were used to validate the effect of TAs-FUW. RESULTS: The UPLC-Q-TOF/MS analysis revealed that TAs-FUW mainly contain six compounds (peiminine, peimine, edpetiline, khasianine, peimisine, and sipeimine). TAs-FUW improved airway inflammation and obstruction, mucus secretion, collagen deposition, and leukocyte and macrophage infiltration, and downregulated TSLP by inhibiting the TRPV1/NFAT pathway in asthmatic mice. In vitro, the application of CPZ demonstrated that the TRPV1 channel is involved in TNF-α/IL-4-mediated regulation of TSLP. TAs-FUW suppressed TNF-α/IL-4-induced TSLP generation expression by regulating the TRPV1/Ca2+/NFAT pathway. Furthermore, TAs-FUW reduced CAP-induced TSLP release by inhibiting TRPV1 activation. Notably, sipeimine and edpetiline each were sufficient to block the TRPV1-mediated Ca2+ influx. CONCLUSION: Our study is the first to demonstrate that TNF-α/IL-4 can activate the TRPV1 channel. TAs-FUW can alleviate asthmatic inflammation by suppressing the TRPV1 pathway and thereby preventing the increase in cellular Ca2+ influx and the subsequent NFAT activation. The alkaloids in FUW may be used for complementary or alternative therapies in asthma.

Proteomic analysis reveals that Polygonatum cyrtonema Hua polysaccharide ameliorates mice muscle atrophy in chemotherapy-induced cachexia.

Polygonatum cyrtonema Hua polysaccharide (PCP) is the main bioactive compound derived from the herb Polygonati Rhizoma, known for its anti-fatigue, antioxidant, immunomodulatory, and anti-inflammatory properties. However, its effectiveness on alleviating chemotherapy-induced muscle atrophy has been unclear. In this study, we utilized proteomic analysis to investigate the effects and mechanisms of PCP on gemcitabine plus cisplatin (GC) induced muscle atrophy in mice. Quality control analysis revealed that the functional PCP, rich in glucose, is a heterogeneous polysaccharide comprised of nine monosaccharides. PCP (64 mg/kg) significantly alleviated body muscle, organ weight loss, and muscle fiber atrophy in chemotherapy-induced cachectic mice. Moreover, PCP suppressed the decrease in serum immunoglobulin levels and the increase in pro-inflammatory factor interleukin-6 (IL-6). Proteomic analysis demonstrated that PCP contributed to the homeostasis of protein metabolism in gastrocnemius muscle. Diacylglycerol kinase (DGKζ) and cathepsin L (CTSL) were identified as primary PCP targets. Furthermore, the IL-6/STAT3/CTSL and DGKζ/FoxO/Atrogin1 signaling pathways were validated. Our findings suggest that PCP exerts an anti-atrophy effect on chemotherapy-induced muscle atrophy by regulating the autophagy-lysosome and ubiquitin-proteasome systems.

The biological roles of CD24 in ovarian cancer: old story, but new tales.

CD24 is a glycosylphosphatidylinositol linked molecular which expressed in diverse malignant tumor cells, particular in ovarian carcinoma cells and ovarian carcinoma stem cells. The CD24 expression is associated with increased metastatic potential and poor prognosis of malignancies. CD24 on the surface of tumor cells could interact with Siglec-10 on the surface of immune cells, to mediate the immune escape of tumor cells. Nowadays, CD24 has been identified as a promising focus for targeting therapy of ovarian cancer. However, the roles of CD24 in tumorigenesis, metastasis, and immune escape are still not clearly demonstrated systematically. In this review, we i) summarized the existing studies on CD24 in diverse cancers including ovarian cancer, ii) illustrated the role of CD24-siglec10 signaling pathway in immune escape, iii) reviewed the existing immunotherapeutic strategies (targeting the CD24 to restore the phagocytic effect of Siglec-10 expressing immune cells) based on the above mechanisms and evaluated the priorities in the future research. These results might provide support for guiding the CD24 immunotherapy as the intervention upon solid tumors.

Myeloid-derived suppressor cells and pulmonary hypertension.

Pulmonary hypertension (PH) is a chronic pulmonary vascular disorder characterized by an increase in pulmonary vascular resistance and pulmonary arterial pressure. The detailed molecular mechanisms remain unclear. In recent decades, increasing evidence shows that altered immune microenvironment, comprised of immune cells, mesenchymal cells, extra-cellular matrix and signaling molecules, might induce the development of PH. Myeloid-derived suppressor cells (MDSCs) have been proposed over 30 years, and the functional importance of MDSCs in the immune system is appreciated recently. MDSCs are a heterogeneous group of cells that expand during cancer, chronic inflammation and infection, which have a remarkable ability to suppress T-cell responses and may exacerbate the development of diseases. Thus, targeting MDSCs has become a novel strategy to overcome immune evasion, especially in tumor immunotherapy. Nowadays, severe PH is accepted as a cancer-like disease, and MDSCs are closely related to the development and prognosis of PH. Here, we review the relationship between MDSCs and PH with respect to immune cells, cytokines, chemokines and metabolism, hoping that the key therapeutic targets of MDSCs can be identified in the treatment of PH, especially in severe PH.

A highly sensitive sensor for carcinoembryonic antigen based on AlGaN/GaN high-electron-mobility transistors.

Carcinoembryonic antigen (CEA) is a well-known biomarker and validated serum biomarker for lung cancer. We introduce a simple label-free method for CEA detection. Specific recognition of CEA was made possible by immobilizing CEA antibodies in the sensing region of AlGaN/GaN high-electron-mobility transistors. The biosensors have a detection limit of 1 fg ml-1in phosphate buffer solution. This approach has advantages of integration, miniaturization, low cost, and rapid detection compared to other testing methods for lung cancer and could be used in future medical diagnostics.

Dietary Methionine Restriction Improves Gastrocnemius Muscle Glucose Metabolism through Improved Insulin Secretion and H19/IRS-1/Akt Pathway in Middle-Aged Mice.

Methionine restriction (MR) improves glucose metabolism. In skeletal muscle, H19 is a key regulator of insulin sensitivity and glucose metabolism. Therefore, this study aims to reveal the underlying mechanism of H19 upon MR on glucose metabolism in skeletal muscle. Middle-aged mice were fed MR diet for 25 weeks. Mouse islets ß cell line ß-TC6 cells and mouse myoblast cell line C2C12 cells were used to establish the apoptosis or insulin resistance model. Our findings showed that MR increased B-cell lymphoma-2 (Bcl-2) expression, deceased Bcl-2 associated X protein (Bax), cleaved cysteinyl aspartate-specific proteinase-3 (Caspase-3) expression in pancreas, and promoted insulin secretion of ß-TC6 cells. Meanwhile, MR increased H19 expression, insulin Receptor Substrate-1/insulin Receptor Substrate-2 (IRS-1/IRS-2) value, protein Kinase B (Akt) phosphorylation, glycogen synthase kinase-3ß (GSK3ß) phosphorylation, and hexokinase 2 (HK2) expression in gastrocnemius muscle and promoted glucose uptake in C2C12 cells. But these results were reversed after H19 knockdown in C2C12 cells. In conclusion, MR alleviates pancreatic apoptosis and promotes insulin secretion. And MR enhances gastrocnemius muscle insulin-dependent glucose uptake and utilization via the H19/IRS-1/Akt pathway, thereby ameliorating blood glucose disorders and insulin resistance in high-fat-diet (HFD) middle-aged mice.

[A preliminary study on the role of V-domain Ig suppressor of T cell activation in juvenile idiopathic arthritis]. / Tç»†èƒžæ´»åŒ–å ç–«çƒè›‹ç™½æŠ‘åˆ¶Våž‹ç»“æž„åŸŸåœ¨å¹¼å¹´ç‰¹å‘æ€§å ³èŠ‚ç‚Žä¸­ä½œç”¨çš„åˆæ­¥ç ”ç©¶.

OBJECTIVES: To study the expression of V-domain Ig suppressor of T cell activation (VISTA) in peripheral blood of children with juvenile idiopathic arthritis (JIA) and its role in the pathogenesis of JIA. METHODS: In this prospective study, peripheral blood was collected from 47 children with different subtypes of JIA and 10 healthy children. Flow cytometry was used to measure the expression levels of VISTA, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) on CD14+ mononuclear cells, CD4+ T lymphocytes, and CD8+ T lymphocytes. RESULTS: The children with JIA had a significantly lower expression level of VISTA than the healthy children (P<0.05). There was a significant difference in the expression of VISTA between the children with different subtypes of JIA, with the lowest expression level in those with systemic JIA (P<0.05). There was also a significant difference in the expression of VISTA between different immune cells, with a significantly higher expression level on the surface of monocytes (P<0.05). Correlation analysis showed that VISTA was negatively correlated with the expression of IFN-γ and TNF-α on CD4+ T cells (r=-0.436 and -0.382 respectively, P<0.05), CD8+ T cells (r=-0.348 and -0.487 respectively, P<0.05), and CD14+ mononuclear cells (r=-0.582 and -0.603 respectively, P<0.05). CONCLUSIONS: The insufficient expression of VISTA may be associated with the pathogenesis of JIA, and enhancing the immunomodulatory effect of VISTA might be one option for the treatment of JIA in the future.