Male reproductive function before and after the adjustment of the COVID-19 prevention policy: a multicenter study in China.

At the end of 2022, the adjustment of the coronavirus disease 2019 (COVID-19) pandemic control policy in China resulted in a large-scale increase in public infection. To compare the fertility parameters of male patients before and after the adjustments of the COVID-19 pandemic control policy in China, we collected data on patients' medical histories and laboratory examinations on their first visits between June 2022 and March 2023 in five different hospitals. Data were divided into five groups according to the timeline of the policy adjustment. The data we collected from male patients included semen quality and serum reproductive hormone levels, and intergroup comparisons were made using the Mann-Whitney U and Chi-square tests. In total, 16 784 cases underwent regular semen analysis, 11 180 had sperm morphology assessments, and 7200 had reproductive hormone analyses. The data showed declining trends in semen volume, sperm motility, and the progressive sperm motility rate after the policy adjustment. Subgroup comparison revealed an initial decrease and gradual recovery in progressive motility rate. Sperm morphology analysis showed increased neck and tail abnormalities after the policy adjustment. No significant change in hormone levels was observed. Following the adjustment of the COVID-19 prevention policy in China, a decline in sperm motility and morphology was observed. This trend may gradually recover over 2 months. After the policy adjustment, reproductive hormone levels were relatively stable throughout, except for an increase in luteinizing hormone (LH). These changes in semen parameters suggest that the policy adjustment had a short- to medium-term impact on male reproductive function.

DEC1 is involved in TGF-ß1-induced epithelial-mesenchymal transition of gastric cancer.

DEC1 is a helix-loop-helix (bHLH) transcription factor, whose deregulation has been observed in several tumors. However, the effects of the dysregulation of this gene on epithelial-mesenchymal transition (EMT) are controversial, with its roles in gastric cancer (GC) remaining unclear. In the present study, we focused on the impact of DEC1 on EMT and cell mobility in gastric cancer. We found that DEC1 expression positively correlated with TGF-ß1 and EMT markers in tumor issues, and that DEC1 facilitated TGF-ß1-induced EMT in gastric cancer. In addition, gastric cancer cell migration potential was reduced after DEC1 knockdown. Using murine metastasis models, we confirmed that DEC1 promoted GC metastasis and further explored the correlation of DEC1 with TGF-ß1 and E-cadherin in vivo. Chromatin immunoprecipitation (ChIP) assays revealed that DEC1 could directly interact with the promoter region of TGF-ß1. These results suggest that DEC1 functions as a tumor enhancer that partially participates in TGF-ß1-mediated EMT processes in GC, thus contributing to tumor metastasis.

Controlling Superhydrophobicity on Complex Substrates Based on a Vapor-Phase Sublimation and Deposition Polymerization.

The superhydrophobic properties of material surfaces have attracted significant research and practical development in a wide range of applications. In the present study, a superhydrophobic coating was fabricated using a vapor-phase sublimation and deposition process. This process offers several advantages, including a controllable and tunable superhydrophobic property, a dry and solvent-free process that uses well-defined water/ice templates during fabrication, and a coating technology that is applicable to various substrates, regardless of their dimensions or complex geometric configurations. The fabrication process exploits time-dependent condensation to produce ice templates with a controlled surface morphology and roughness. The templates are sacrificed via vapor sublimation, which results in mass transfer of water vapor out of the system. A second vapor source of a polymer precursor is then introduced to the system, and deposition occurs upon polymerization on the iced templates, replicating the same topologies from the iced templates. The continuation of the co-current sublimation and deposition processes finally renders permanent hierarchical structures of the polymer coatings that combine the native hydrophobic property of the polymer and the structured property by the sacrificed ice templates, achieving a level of superhydrophobicity that is tunable from 90° to 164°. The experiments demonstrated the use of [2,2]paracyclophanes as the starting materials for forming the superhydrophobic coatings of poly(p-xylylenes) on substrate surfaces. In comparison to conventional vapor deposition of poly(p-xylylenes), which resulted in dense thin-film coatings with only a moderate water contact angle of approximately 90°, the reported superhydrophobic coatings and fabrication process can achieve a high water contact angle of 164°. Demonstrations furthermore revealed that the proposed coatings are durable while maintaining superhydrophobicity on various substrates, including an intraocular lens and a cardiovascular stent, even against harsh treatment conditions and varied solution compositions used on the substrates.

Deleted in lymphocytic leukemia 2 (DLEU2): a possible biomarker that holds promise for future diagnosis and treatment of cancer.

The mechanism of deleted in lymphocytic leukemia 2 (DLEU2)-long non-coding RNA in tumors has become a major point of interest in recent research related to the occurrence and development of a variety of tumors. Recent studies have shown that the long non-coding RNA DLEU2 (lncRNA-DLEU2) can cause abnormal gene or protein expression by acting on downstream targets in cancers. At present, most lncRNA-DLEU2 play the role of oncogenes in different tumors, which are mostly associated with tumor characteristics, such as proliferation, migration, invasion, and apoptosis. The data thus far show that because lncRNA-DLEU2 plays an important role in most tumors, targeting abnormal lncRNA-DLEU2 may be an effective treatment strategy for early diagnosis and improving the prognosis of patients. In this review, we integrated lncRNA-DLEU2 expression in tumors, its biological functions, molecular mechanisms, and the utility of DLEU2 as an effective diagnostic and prognostic marker of tumors. This study aimed to provide a potential direction for the diagnosis, prognosis, and treatment of tumors using lncRNA-DLEU2 as a biomarker and therapeutic target.

Chemical Characterization and Atherosclerosis Alleviation Effects of Gypenosides from Gynostemma pentaphyllum through Ameliorating Endothelial Dysfunction via the PCSK9/LOX-1 Pathway.

Dietary saponins have the potential to ameliorate atherosclerosis (AS). Gypenosides of Gynostemma pentaphyllum (GPs) have been used as functional foods to exhibit antiatherosclerotic activity. The present study aimed to explore the protective effect, underlying mechanism and active substances of GPs on AS in vivo and in vitro. Results demonstrated GPs administration reduced the serum concentrations of TC and LDL-C, upregulated the plasma HDL-C content, inhibited the secretion of ICAM-1, VCAM-1, and MCP-1, and alleviated vascular lesions in VitD3 plus high cholesterol diet-induced AS rats as well as reduced adhesion factors levels in ox-LDL-stimulated HUVECs, which was potentially associated with suppressing PCSK9/LOX-1 pathway. Further activity-guided phytochemical investigation of GPs led to the identification of five new dammarane-type glycosides (1-5) and ten known analogs (6-15). Bioassay evaluation showed compounds 1, 6, 7, 12, 13, and 14 observably reduced the expressions of PCSK9 and LOX-1, as well as the secretion of adhesion factors in injured HUVECs. Molecular docking experiments suggested that the active saponins of GPs might bind to the allosteric pocket of PCSK9 located at the catalytic and C-terminal domains, and 2α-OH-protopanaxadiol-type gypenosides might exert a higher affinity for an allosteric binding site on PCSK9 by hydrogen-bond interaction with ARG-458. These findings provide new insights into the potential nutraceutical application of GPs and their bioactive compounds in the prevention and discovery of novel therapeutic strategies for AS.

Dammarane-type saponins with proprotein convertase subtilisin/kexin type 9 inhibitory activity from Gynostemma pentaphyllum.

Seven undescribed dammarane-type saponins, gypenosides LXXXI-LXXXVII, together with four known compounds, were isolated from the whole herb of Gynostemma pentaphyllum. The chemical structures of these undescribed compounds were elucidated on the basis of physical and spectroscopic analysis and comparison with literature data. All the isolates were evaluated for their proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitory activities in HepG2 cells. Among them, gypenosides LXXXII-LXXXVII, gynosaponin II, IV and VI suppressed the expression of PCSK9 in LPDS-induced HepG2 cells at 20 µM; gypenosides LXXXII, LXXXV and LXXXVII showed inhibitory activities against PCSK9 at 10 µM; notably, gypenoside LXXXII still exhibited inhibitory activity against PCSK9 at 5 µM.

The Function of cGAS-STING Pathway in Treatment of Pancreatic Cancer.

The activation of stimulator of interferon genes (STING) signalling pathway has been suggested to promote the immune responses against malignancy. STING is activated in response to the detection of cytosolic DNA and can induce type I interferons and link innate immunity with the adaptive immune system. Due to accretive evidence demonstrating that the STING pathway regulates the immune cells of the tumor microenvironment (TME), STING as a cancer biotherapy has attracted considerable attention. Pancreatic cancer, with a highly immunosuppressive TME, remains fatal cancer. STING has been applied to the treatment of pancreatic cancer through distinct strategies. This review reveals the role of STING signalling on pancreatic tumors and other diseases related to the pancreas. We then discuss new advances of STING in either monotherapy or combination methods for pancreatic cancer immunotherapy.

Comparison of the Cytokine Profile in Mesenchymal Stem Cells from Human Adipose, Umbilical Cord, and Placental Tissues.

Human mesenchymal stem cells (MSCs) can be isolated from various tissues. However, the cytokine profile in different MSC types remains unclear. In this study, MSCs were extracted from adipose, umbilical cord, and placental tissues. The surface marker expression, multilineage differentiation potential, and cytokine secretion of these cells were compared. The isolated MSCs exhibited similar morphology and surface marker expression. However, they differed with regard to their differentiation potential. Adipose-MSCs (A-MSCs) exhibited a higher potential for adipogenesis and osteogenic differentiation compared with umbilical cord-MSCs (UC-MSCs) and placental-MSCs (P-MSCs). The expression levels of 80 cytokines were detected, and the data demonstrated that the three MSC types abundantly secreted insulin-like growth factor-binding protein (IGFBP)-4, IGFBP-3, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, IGFBP-6, monocyte chemoattractant protein-1, and granulocyte colony-stimulating factor. However, the expression levels of vascular endothelial growth factor, tumor necrosis factor alpha, interleukin (IL)-6 receptor, and IL-13 in A-MSCs were higher compared with those of UC-MSCs and P-MSCs. Moreover, the expression levels of intercellular adhesion molecule-1 and growth differentiation factor 15 were lower in A-MSCs. Kyoto Encyclopedia of Genes and Genomes analysis indicated that the "adipocytokine" and the "PI3K/Akt pathways" were enriched in A-MSCs. Taken together, the results demonstrated that MSCs from different sources exhibited differences in the secretion of specific factors. A-MSCs were associated with the expression of several proangiogenic factors and may be an improved source for angiogenesis and tissue regeneration.

Gypenoside LVI improves hepatic LDL uptake by decreasing PCSK9 and upregulating LDLR expression.

BACKGROUNDS: Atherosclerotic Cardiovascular Disease (ASCVD) is defined as ischemic or endothelial dysfunction-various inflammatory diseases, which is mainly caused by excessive low-density lipoprotein cholesterol (LDL-C) in circulating blood. Gynostemma pentaphyllum is a traditional Chinese medicine, and total Gypenosides are used for the treatment of hyperlipidemia and to reduce circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) level. However, which gypenoside involved in the modulation of PCSK9 expression is still unknown. PURPOSE: This study aimed to discover effective PCSK9 inhibitors from Gypenosides in accordance with the 2019 ESC/EAS guidelines. METHODS: HPLC was employed to determine major six components of Gypenosides. The inhibitory activity on secreted PCSK9 in HepG2 of six major compounds from Gypenosides were screened by ELISA. The level of low-density lipoprotein (LDL) receptor (LDLR) was determined by Flow cytometry and Immunofluorescence. The expression levels of PCSK9, LDLR and Sterol-regulatory element binding proteins-2 (SREBP-2) were analyzed by qPCR and Western blot. DiI-LDL was added to evaluated LDL uptake into HepG2. RESULTS: The results suggested that the mRNA and protein levels of PCSK9 were down-regulated by Gypenoside LVI and the LDLR degradation in lysosomes system was inhibited, thereby leading to an increasing in LDL uptake into HepG2 cells. Furthermore, Gypenoside LVI decreased PCSK9 expression induced by stains. Altogether, Gypenoside LVI enhances LDL uptake into HepG2 cells by increased LDLR level on cell-surface and suppressed PCSK9 expression. CONCLUSION: This indicates that Gypenoside LVI can be used as a useful supplement for statins in the treatment of hypercholesterolemia. This is firstly reported that monomeric compound of G. pentaphyllum planted in Hunan province has the effect of increasing LDL-C uptake in hepatocytes via inhibiting PCSK9 expression.

New dammarane-type glycosides from Gynostemma pentaphyllum and their lipid-lowering activity.

Gynostemma pentaphyllum (Thunb.) Makino has a long history as food and diary supplement in China. At present, there are some products for hyperlipidemia in the market, including G. pentaphyllum tea, healthy wine and healthy food. In order to discover proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, fourteen new triterpenoid saponins named gypenoside LXXXVIII-CI (1-14) along with six known compounds (15-20) were isolated from G. pentaphyllum. Their structures were elucidated by means of various spectroscopic techniques. Eight isolates were evaluated the inhibitory effect on PCSK9 in HepG2 cells. The results showed that three dammarane-type glycosides (2, 3, 15) remarkably reduced PCSK9 expression at 10 µM concentration. These findings suggested that G. pentaphyllum was worthy of further investigation to find small molecule PCSK9 inhibitors and facilitate their utilization as functional food ingredients.

Adipose-derived stromal cells improve functional recovery after spinal cord injury through TGF-ß1/Smad3/PLOD2 pathway activation.

Transplantation of mesenchymal stromal cells (MSCs) improves functional recovery in experimental models of spinal cord injury (SCI), but the mechanism is not fully understood. Activation of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a collagen-modifying enzyme, reportedly follows MSC transplantation in an SCI animal model. We investigated the regulation of PLOD2 expression and its potential contribution to the neuroprotective effects of adipose-derived stromal cells (ADSCs) following mechanical injury to neurons in vitro and SCI in vivo. ADSCs enhanced wound healing in vitro and promoted functional recovery after their implantation near injury sites in a rat SCI model. These effects correlated with upregulation of PLOD2, MAP2, NSE and GAP43, and downregulation of GFAP, which is indicative of improved neuronal survival and axonal regeneration as well as reduced glial scar formation. The neurorestorative effect of ADSCs was weakened after inhibition of PLOD2 expression. ADSCs appeared to induce PLOD2 upregulation via TGF-ß1 secretion, as ADSC-mediated PLOD2 expression, neuronal survival, and functional recovery after SCI were largely prevented by SB431542, a TGF-(1 receptor inhibitor. These findings indicate that ADSCs reduce lesion size and promote functional recovery after SCI mainly through activation of a TGF-ß1/P-Samd3/PLOD2 pathway in spinal cord neurons.

Development of a Novel Serum Exosomal MicroRNA Nomogram for the Preoperative Prediction of Lymph Node Metastasis in Esophageal Squamous Cell Carcinoma.

Preoperative prediction of lymph node (LN) metastasis is accepted as a crucial independent risk factor for treatment decision-making for esophageal squamous cell carcinoma (ESCC) patients. Our study aimed to establish a non-invasive nomogram to identify LN metastasis preoperatively in ESCC patients. Construction of the nomogram involved three sequential phases with independent patient cohorts. In the discovery phase (N = 20), LN metastasis-associated microRNAs (miRNAs) were selected from next-generation sequencing (NGS) assay of human ESCC serum exosome samples. In the training phase (N = 178), a nomogram that incorporated exosomal miRNA model and clinicopathologic was developed by multivariate logistic regression analysis to preoperatively predict LN status. In the validation phase (n = 188), we validated the predicted nomogram's calibration, discrimination, and clinical usefulness. Four differently expressed miRNAs (chr 8-23234-3p, chr 1-17695-5p, chr 8-2743-5p, and miR-432-5p) were tested and selected in the serum exosome samples from ESCC patients who have or do not have LN metastasis. Subsequently, an optimized four-exosomal miRNA model was constructed and validated in the clinical samples, which could effectively identify ESCC patients with LN metastasis, and was significantly superior to preoperative computed tomography (CT) report. In addition, a clinical nomogram consisting of the four-exosomal miRNA model and CT report was established in training cohort, which showed high predictive value in both training and validation cohorts [area under the receiver operating characteristic curve (AUC): 0.880 and 0.869, respectively]. The Hosmer-Lemeshow test and decision curve analysis implied the nomogram's clinical applicability. Our novel non-invasive nomogram is a robust prediction tool with promising clinical potential for preoperative LN metastasis prediction of ESCC patients, especially in T1 stage.

Loss of SIRT4 promotes the self-renewal of Breast Cancer Stem Cells.

Rationale: It has been proposed that cancer stem/progenitor cells (or tumor-initiating cells, TICs) account for breast cancer initiation and progression. Sirtuins are nicotinamide adenine dinucleotide (NAD+)-dependent class-III histone deacetylases and mediate various basic biological processes, including metabolic homeostasis. However, interplay and cross-regulation among the sirtuin family are not fully understood. As one of the least studied sirtuin family members, the mitochondrial sirtuin SIRT4 is a tumor suppressor gene in various cancers. However, its role in cancer stemness, as well as initiation and progression of breast cancer, remains unknown. Methods: The expression of SIRT4 in breast cancer was analyzed using the TCGA breast cancer database and 3 GSEA data. Normal breast epithelial cells MCF10A and breast cancer cell lines MCF-7, MDA-MB-231, BT549, MDA-MB-468 were used to establish SIRT4 gene knockdown and corresponding overexpression cells. Identified MTT cytotoxicity assays, cell invasion and motility assay, sorting of SP, confocal immunofluorescence microscopy, mouse mammary stem cell analysis, glutamine and glucose production, clonogenic and sphere-formation assay, mass spectrometric metabolomics analysis and ChIP-seq to further explore SIRT4 biological role in breast cancer. Results: We elucidated a novel role for SIRT4 in the negative regulation of mammary gland development and stemness, which is related to the mammary tumorigenesis. We also uncovered an inverse correlation between SIRT4 and SIRT1. Most importantly, SIRT4 negatively regulates SIRT1 expression via repressing glutamine metabolism. Besides, we identified H4K16ac and BRCA1 as new prime targets of SIRT4 in breast cancer. Conclusions: These results demonstrate that SIRT4 exerts its tumor-suppressive activity via modulating SIRT1 expression in breast cancer and provide a novel cross-talk between mitochondrial and nuclear sirtuins.

The involvement of exosomes in the diagnosis and treatment of pancreatic cancer.

At the moment, pancreatic cancer is among the deadliest gastrointestinal diseases, and pancreatic cancer growth is a complex biological process that is based on different kinds of genes. Exosomes are extracellular vesicles containing microRNAs (miRNAs), messenger RNA (mRNA), and proteins, they act as the most prominent mediator of intercellular communication, and they regulate, instruct, and re-educate their surrounding microenvironment and target specific organs. Due to accumulative evidence proved that exosomes are involved in metastasis, cell proliferation, EMT, angiogenesis, and TME of pancreatic cancer, exosomes are crucial potential candidates to detect pancreatic cancer early. This review aims to convey the current understanding of the main functions employed by exosomes in early diagnosis and treatment of pancreatic cancer.

HYR-2 plays an anti-lung cancer role by regulating PD-L1 and Akkermansia muciniphila.

Traditional Chinese medicine (TCM) plays a vital part in cancer treatment due to its unique superiority. Huoxue Yiqi Recipe-2 (HYR-2) was supposed to have therapeutic effect on lung cancer, which came from Ze Qi Decoction in one of the four great classics of TCM called "Synopsis of Prescriptions of the Golden Chamber". Network pharmacology demonstrated that the targets of active components from HYR-2 were significantly enriched in the signaling pathways, which were closely associated with non-small cell lung cancer (NSCLC) and programmed death ligand 1 (PD-L1). Then, data about NSCLC was downloaded from Gene Expression Omnibus database (GEO). The Cancer Genome Atlas (TCGA) and DisGeNET was analyzed by bioinformatics, and 214 biomarkers for NSCLC were obtained, containing 14 targets of active components from HYR-2 (which were significantly enriched in the PD-L1 related signaling pathway). In vivo and in vitro experiments showed that HYR and HYR-2 could inhibit the growth of lung cancer and down-regulate the expression of PD-L1, which might be related to the blocking effect of HYR-2 on the PI3K/Akt signaling pathway. Furthermore, HYR-2 promoted the transformation of M2 macrophages into M1 macrophages as well. It is deserved to be mentioned that the level of Akkermansia muciniphila was also significantly elevated by HYR-2, which was believed to enhance the therapeutic effect of PD-L1 antibodies. To sum up, HYR-2 might play an anti-lung cancer effect by down-regulating PD-L1 together with up-regulating Akkermansia muciniphila.

Holliday junction recognition protein promotes pancreatic cancer growth and metastasis via modulation of the MDM2/p53 signaling.

Holliday junction recognition protein (HJURP) refers to a histone H3 chaperone that has been implicated in different kinds of malignancies. Yet, its character in pancreatic cancer remains unclear. The expression of HJURP was assessed in PDAC tissues by RT-qPCR, immunoblotting, and immunohistochemistry. HJURP-deficient or overexpressed PDAC cell lines were constructed, using shRNA or plasmids with HJURP insert. MTT, sphere formation assay, migration, and invasion assays were performed to evaluate the viability, proliferation, migration, and invasion of PDAC cells. We used xenograft mice models to assess the tumor growth and metastasis in vivo. RNA-seq was applicated in search of the potential downstream target of HJURP in PDAC and subsequent verification were fulfilled via multiple assays, including immunofluorescence. Additionally, chromatin immunoprecipitation and luciferase reporter assay were conducted to explore the potential regulation of MDM2 expression by HJURP through H3K4me2. In this current research, we found that the expression of HJURP in PDAC cells and tissue was significantly higher than those of adjacent normal tissue, and high HJURP expression predicted poor survival. HJURP significantly promoted the viability, sphere formation, migration, and invasion of PDAC cells in vitro, HJURP also facilitated tumor growth and metastasis in vivo. Mechanically, MDM2/p53 axis is critical for HJURP-mediated malignant behaviors in PDAC, and HJURP regulates MDM2 expression through H3K4me2. HJURP could serve as a promising biomarker, and target for PDAC prognosis and treatment.

Expression levels and associations of five long non-coding RNAs in gastric cancer and their clinical significance.

Gastric cancer (GC) is a type of cancer that is commonly diagnosed worldwide due to a lack of early diagnostic, prognostic and therapeutic targets for this disease. The aim of the present study was to examine the expression levels of five long non-coding RNAs, namely PTPRG antisense RNA 1 (PTPRG-AS1), forkhead box P4 antisense RNA 1 (FOXP4-AS1), bladder cancer-associated transcript 2 (BLACAT2), ZXF2 and upregulated in colorectal cancer (UCC), to study their associations with patient characteristics and assess their prognostic efficacy, in order to determine the possibility of their application as GC biomarkers. The expression levels of long non-coding RNAs (lncRNAs) were determined by reverse transcription-quantitative PCR analysis of 61 pairs of GC tissues and adjacent healthy gastric mucosa tissues and GC cell lines. The Chi-square test was conducted to assess the associations of lncRNA expression levels with clinical characteristics of patients. The effect of UCC on GC cell proliferation was determined using in vitro functional experiments. The prognostic efficacy of FOXP4-AS1, BLACAT2 and UCC were examined in the Gene Expression Profiling Interactive Analysis database and those of PTPRG-AS1 were examined in the Kaplan Meier Plot database. Gene alteration frequencies of PTPRG-AS1 and BLACAT2 in GC were identified using the cBioPortal for Cancer Genomics. PTPRG-AS1, FOXP4-AS1, BLACAT2, ZXF2 and UCC were found to be upregulated in GC cell lines and GC tissues compared with adjacent normal tissues. PTPRG-AS1 and ZXF2 expression levels were associated with the expression status of the cell proliferation marker Ki67. UCC promoted the proliferation of GC cells in vitro and was associated with lymph node metastasis. Increased expression of FOXP4-AS1 indicated a favorable outcome in terms of disease-free survival, whereas high expression of PTPRG-AS1 was associated with poor survival rates for patients in different GC risk groups. BLACAT2 gene mutation was associated with poor disease-free survival outcome for patients with GC. The results suggest that PTPRG-AS1, FOXP4-AS1, BLACAT2, ZXF2 and UCC are potential biomarkers for the detection of GC at the molecular level and may be used as potential targets for GC therapy. The individual roles of these lncRNAs may be utilized for prognostic predictions.

The neuroprotective effect of mesenchymal stem cells is mediated through inhibition of apoptosis in hypoxic ischemic injury.

BACKGROUND: Neonatal hypoxia ischemia causes severe brain damage. Stem cell therapy is a promising method for treating neuronal diseases. Clinical translation of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) for the recovery of neurons after hypoxic ischemic encephalopathy (HIE) may represent an effective therapy. METHODS: Primary neurons were exposed to oxygen-glucose deprivation (OGD) and subsequently cocultured with UC-MSCs. Apoptosis was examined by Annexin V-FITC-PI. Genes related to apoptosis were detected using RT-PCR and western-blot analyses. Using an in vivo model, HIE was induced in postnatal day 7 mice, and UC-MSCs were transplanted via the intraventricular route. UC-MSC migration was investigated by immunofluorescence, and lesion volumes were measured by TTC staining. Apoptosis in injured brain cells was detected by the TUNEL assay. RT-PCR and ELISA were used to detect the expression of inflammatory factors in cells and animal tissues. RESULTS: Flow cytometry analysis revealed that apoptosis in injured neurons was inhibited by UC-MSCs. The RT-PCR and western blot results indicated that coculture inhibited the expression of proapoptotic genes and upregulated expression of antiapoptotic genes. In the animal model, transplanted UC-MSCs migrated toward the cerebral lesion site and decreased the lesion extent in HIE. TUNEL staining showed that the MSC group exhibited significantly reduced numbers of TUNEL-positive cells. RT-PCR and ELISA showed that UC-MSCs inhibited the upregulation of TNF-α and IL-1ß in response to hypoxic ischemic injury. CONCLUSION: These results indicate that UC-MSCs exert neuroprotective effects against hypoxic ischemic injury by inhibiting apoptosis, and the mechanism appears to be through alleviating the inflammatory response.

Advances of immune checkpoints in colorectal cancer treatment.

Colorectal cancer (CRC) is a malignant gastrointestinal cancer that seriously threatens human health. Its morbidity and mortality are in the forefront of tumors. Chemotherapy and radiotherapy play an important role in the treatment of CRC, which can improve the survival time and quality of life of patients, but the treatment progress is slow, and the treatment effect is not satisfactory. In recent years, immunotherapy has been a new direction in the field of colorectal cancer treatment after radiotherapy, chemotherapy and targeted therapy. Immune checkpoints play a vital role in the immunotherapy of cancer, and take part in the immune escape of cancer, which is closely related to the occurrence and development of cancer. This article reviews the research progress of immune checkpoints and their blockers in the field of CRC, in order to help better use of the immune system to treat cancer.

Differences between KC and KPC pancreatic ductal adenocarcinoma mice models, in terms of their modeling biology and their clinical relevance.

Pancreatic ductal adenocarcinoma (PDAC) is among the dangerous human cancers, is the 10th highly prevalent cancer, and the fourth sole cause of cancer-related mortality in the United States of America. Notwithstanding the significant commitment, the forecast for people with this burden continues to have a five-year survival rate of just 4-6%. The most critical altered genes within PDAC consist of K-ras the proto-oncogene which is usually mutationally activated above 90% cases and tumor suppressors likeTrp53 are altered at 55%. To face the burden of pancreatic ductal adenocarcinoma, a variety of genetically engineered pancreatic cancer mice models have been created over the last past years. These models have distinctive features and are not all appropriate for preclinical studies. In this review, we focus on differences between two mice models K-rasLSL.G12D/+;Pdx-1-Cre(KC) and K-rasLSL.G12D/+; Trp53R172H/+; Pdx-1-Cre(KPC) in terms of their modeling biology and their clinical relevance.