Ononin promotes radiosensitivity in lung cancer by inhibiting HIF-1α/VEGF pathway.

BACKGROUND: In our previous study, we provided evidence that Astragalus mongholicus Bunge(AM) and its extracts possess a protective capability against radiation-induced damage, potentially mediated through the reduction of reactive oxygen species (ROS) and nitric oxide (NO). However, we were pleasantly surprised to discover during our experimentation that AM not only offers protection against radiation damage but also exhibits a radiation sensitization effect. This effect may be attributed to a specific small molecule present in AM known as ononin. Currently, radiation sensitizers are predominantly found in nitrazole drugs and nanomaterials, with no existing reports on the radiation sensitization properties of ononin, nor its underlying mechanism. PURPOSE: This study aims to investigate the sensitization effect of the small molecule ononin derived from AM on lung cancer radiotherapy, elucidating its specific molecular mechanism of action. Additionally, the safety profile of combining astragalus small molecule ononin with radiation therapy will be evaluated. METHODS: The effective concentration of ononin was determined through cell survival experiments, and the impact of ononin combined with varying doses of radiation on lung cancer cells was observed using CCK-8 and cell cloning experiments. The apoptotic effect of ononin combined with radiation on lung cancer cells was assessed using Hochester staining, flow cytometry, and WB assay. Additionally, WB and immunofluorescence analysis were conducted to investigate the influence of ononin on HIF-1α/VEGF pathway. Furthermore, Molecular Dynamics Simulation was employed to validate the targeted binding ability of ononin and HIF-1α. A lung cancer cell line was established to investigate the effects of knockdown and overexpression of HIF-1α. Subsequently, the experiment was repeated using tumor bearing nude mice and C57BL/6 mouse models in an in vivo study. Tumor volume was measured using a vernier caliper, while HE, immunohistochemistry, and immunofluorescence techniques were employed to observe the effects of ononin combined with radiation on tumor morphology, proliferation, and apoptosis. Additionally, Immunofluorescence was employed to examine the impact of ononin on HIF-1α/VEGF pathway in vivo, and its effect on liver function in mice was assessed through biochemistry analysis. RESULTS: At a concentration of 25 µM, ononin did not affect the proliferation of lung epithelial cells but inhibited the survival of lung cancer cells. In vitro experiments demonstrated that the combination of ononin and radiation could effectively inhibit the growth of lung cancer cells, induce apoptosis, and suppress the excessive activation of the Hypoxia inducible factor 1 alpha/Vascular endothelial growth factor pathway. In vivo experiments showed that the combination of ononin and radiation reduced the size and proliferation of lung cancer tumors, promoted cancer cell apoptosis, mitigated abnormal activation of the Hypoxia inducible factor 1 alpha pathway, and protected against liver function damage. CONCLUSION: This study provides evidence that the combination of AM and its small molecule ononin can enhance the sensitivity of lung cancer to radiation. Additionally, it has been observed that this combination can specifically target HIF-1α and exert its effects. Notably, ononin exhibits the unique ability to protect liver function from damage while simultaneously enhancing the tumor-killing effects of radiation, thereby demonstrating a synergistic and detoxifying role in tumor radiotherapy. These findings contribute to the establishment of a solid basis for the development of novel radiation sensitizers derived from traditional Chinese medicine.

Cistanche deserticola polysaccharide-functionalized dendritic fibrous nano-silica as oral vaccine adjuvant delivery enhancing both the mucosal and systemic immunity.

Oral vaccines are a safe and convenient alternative to injected vaccines and have great potential to prevent major infectious diseases. However, the harsh gastrointestinal (GI) environment, mucus barriers, low immunogenicity, and lack of effective and safe mucosal adjuvants are the major challenges for oral vaccine delivery. In recent years, nanoparticle-based strategies have become attractive for improving oral vaccine delivery. Here, the dendritic fibrous nano-silica (DFNS) grafted with Cistanche deserticola polysaccharide (CDP) nanoparticles (CDP-DFNS) were prepared and investigated how to impact the immune responses. CDP-DFNS facilitated the antigen uptake in mouse bone marrow-derived dendritic cells (BMDCs), and induce the activation of DCs in vitro. Furthermore, in vivo experiments, the result showed that the uptake efficiency by Peyer's patches (PPs) of CDP-DFNS/BSA was the best. And CDP-DFNS/BSA then significantly activated the DCs in lamina propria (LP), and T/B cells in PPs and mesenteric lymph nodes (MLNs). Moreover, the memory T cell responses in later period of vaccination was stronger than other groups. In addition, CDP-DFNS/BSA enhanced BSA-specific antibody IgG, IgA production, and SIgA secretion, was effective at inducing a strong mixed Th1/Th2 response and mucosal antibody responses. These results indicated that CDP-DFNS deserves further consideration as an oral vaccine adjuvant delivery system.

Effects of selenium nanoparticles produced by Lactobacillus acidophilus HN23 on lipid deposition in WRL68 cells.

Selenium is an essential trace element for most organisms, protecting cells from oxidative damage caused by free radicals and serving as an adjunctive treatment for non-alcoholic fatty liver disease (NAFLD). In this study, We used the lactic acid bacterium Lactobacillus acidophilus HN23 to reduce tetra-valent sodium selenite into particulate matter, and analyzed it through inductively coupled plasma mass spectrometry (ICP-MS), scanning electron microscopy (SEM), X-ray diffraction energy dispersive spectrometry (EDS), and Fourier transform infrared spectroscopy (FTIR). We found that it consisted of selenium nanoparticles (SeNPs) with a mass composition of 65.8 % zero-valent selenium and some polysaccharide and polypeptide compounds, with particle sizes ranging from 60 to 300 nm. We also detected that SeNPs were much less toxic to cells than selenite. We further used free fatty acids (FFA)-induced WRL68 fatty liver cell model to study the therapeutic effect of SeNPs on NAFLD. The results show that SeNPs are more effective than selenite in reducing lipid deposition, increasing mitochondrial membrane potential (MMP) and antioxidant capacity of WRL68 cells, which is attributed to the chemical valence state of selenium and organic composition in SeNPs. In conclusion, SeNPs produced by probiotics L. acidophilus had the potential to alleviate NAFLD by reducing hepatocyte lipid deposition and oxidative damage. This study may open a new avenue for SeNPs drug development to treat NAFLD.

Upregulation of tumor suppressor PIAS3 by Honokiol promotes tumor cell apoptosis via selective inhibition of STAT3 tyrosine 705 phosphorylation.

The natural product Honokiol exhibits robust antitumor activity against a range of cancers, and it has also received approval to undergo phase I clinical trial testing. We confrmed that honokiol can promote the apoptotic death of tumor cells through cell experiments. Then siRNA constructs specific for PIAS3, PIAS3 overexpression plasmid and the mutation of the STAT3 Tyr705 residue were used to confirm the mechanism of Honokiol-induced apoptosis. Finally, we confrmed that honokiol can promote PIAS3 upregulation, in turn suppressing STAT3 Tyr705 phosphorylation through the in vivo and in vitro experiments. Honokiol was ultimately found to reduce tumor cell viability by promoting apoptosis through a mechanism dependent on the ability of Honokiol to promote PIAS3 upregulation and the selective inhibition of p-STAT3 (Tyr705) without affecting p-STAT3 (Ser727) or p-STAT1 (Tyr701) levels. PIAS3 knockdown and overexpression in tumor cells altered STAT3 activation and associated DNA binding activity through the control of Tyr705 phosphorylation via PIAS3-STAT3 complex formation, ultimately shaping Honokiol-induced tumor cell apoptosis. Honokiol was also confirmed to significantly prolong the survival of mice bearing xenograft tumors in a PIAS3-dependent fashion. Together, these findings highlight a novel pathway through which Honokiol can promote PIAS3 upregulation, in turn suppressing STAT3 Tyr705 phosphorylation and promoting the apoptotic death of tumor cells.

[Effect of Suanzaoren Decoction on expression of ionotropic glutamate receptors and synaptic plasticity in hippocampus of anxiety rats].

This study investigated the effect of Suanzaoren Decoction on the expression of N-methyl-D-aspartate receptors(NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors(AMPAR) in the hippocampus and synaptic plasticity in rats with conditioned fear-induced anxiety. The effect of Suanzaoren Decoction on rat behaviors were evaluated through open field experiment, elevated plus maze experiment, and light/dark box experiment. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of glutamate(Glu) and γ-aminobutyric acid(GABA) in the rat hippocampus. Real-time fluorescence quantitative PCR(qRT-PCR) and Western blot were employed to assess the gene and protein expression of ionotropic glutamate receptors in the hippocampal region. Transmission electron microscopy was utilized to observe the changes in the ultrastructure of synaptic neurons in the hippocampal region. Long-term potentiation(LTP) detection technique was employed to record the changes in population spike(PS) amplitude in the hippocampal region of mice in each group. The behavioral results showed that compared with the model group, the Suanzaoren Decoction group effectively increased the number of entries into open arms, time spent in open arms, percentage of time spent in open arms out of total movement time, number of entries into open arms out of total entries into both arms(P<0.01), and significantly increased the time spent in the light box and the number of shuttle crossings(P<0.01). There was an increasing trend in the number of grid crossings, entries into the center grid, and time spent in the center grid, indicating a significant anxiolytic effect. ELISA results showed that compared with the model group, the Suanzaoren Decoction group exhibited significantly reduced levels of Glu, Glu/GABA ratio(P<0.01), and significantly increased levels of GABA(P<0.01) in the rat hippocampus. Furthermore, Suanzaoren Decoction significantly decreased the gene and protein expression of NMDAR(GluN2B and GluN2A) and AMPAR(GluA1 and GluA2) compared with the model group. Transmission electron microscopy results demonstrated improvements in synapses, neuronal cells, and organelles in the hippocampal region of the Suanzaoren Decoction group compared with the model group. LTP detection results showed a significant increase in the PS amplitude changes in the hippocampal region of Suanzaoren Decoction group from 5 to 35 min compared with the model group(P<0.05, P<0.01). In conclusion, Suanzaoren Decoction exhibits significant anxiolytic effects, which may be attributed to the reduction in NMDAR and AMPAR expression levels and the improvement of synaptic plasticity.

Combining hybrid nanoflowers with hybridization chain reaction for highly sensitive detection of SARS-CoV-2 nucleocapsid protein.

BACKGROUND: COVID-19 (coronavirus disease 2019) pandemic has had enormous social and economic impacts so far. The nucleocapsid protein (N protein) is highly conserved and is a key antigenic marker for the diagnosis of early SARS-CoV-2 infection. RESULTS: In this study, the N protein was first captured by an aptamer (Aptamer 58) coupled to magnetic beads (MBs), which in turn were bound to another DNA sequence containing the aptamer (Aptamer 48-Initiator). After adding 5'-biotinylated hairpin DNA Amplifier 1 and Amplifier 2 with cohesive ends for complementary hybridization, the Initiator in the Aptamer 48-Initiator began to trigger the hybridization chain reaction (HCR), generating multiple biotin-labeled DNA concatamers. When incubated with synthetic streptavidin-invertase-Ca3(PO4)2 hybrid nanoflower (SICa), DNA concatamers could specifically bind to SICa through biotin-streptavidin interaction with high affinity. After adding sucrose, invertase in SICa hydrolyzed sucrose to glucose, whose concentration could be directly read with a portable glucometer, and its concentration was positively correlated with the amount of captured N protein. The method is highly sensitive with a detection limit as low as 1 pg/mL. SIGNIFICANCE: We believe this study provided a practical solution for the early detection of SARS-CoV-2 infection, and offered a new method for detecting other viruses through different target proteins.

Asymmetric response of aboveground and belowground temporal stability to nitrogen and phosphorus addition in a Tibetan alpine grassland.

Anthropogenic eutrophication is known to impair the stability of aboveground net primary productivity (ANPP), but its effects on the stability of belowground (BNPP) and total (TNPP) net primary productivity remain poorly understood. Based on a nitrogen and phosphorus addition experiment in a Tibetan alpine grassland, we show that nitrogen addition had little impact on the temporal stability of ANPP, BNPP, and TNPP, whereas phosphorus addition reduced the temporal stability of BNPP and TNPP, but not ANPP. Significant interactive effects of nitrogen and phosphorus addition were observed on the stability of ANPP because of the opposite phosphorus effects under ambient and enriched nitrogen conditions. We found that the stability of TNPP was primarily driven by that of BNPP rather than that of ANPP. The responses of BNPP stability cannot be predicted by those of ANPP stability, as the variations in responses of ANPP and BNPP to enriched nutrient, with ANPP increased while BNPP remained unaffected, resulted in asymmetric responses in their stability. The dynamics of grasses, the most abundant plant functional group, instead of community species diversity, largely contributed to the ANPP stability. Under the enriched nutrient condition, the synchronization of grasses reduced the grass stability, while the latter had a significant but weak negative impact on the BNPP stability. These findings challenge the prevalent view that species diversity regulates the responses of ecosystem stability to nutrient enrichment. Our findings also suggest that the ecological consequences of nutrient enrichment on ecosystem stability cannot be accurately predicted from the responses of aboveground components and highlight the need for a better understanding of the belowground ecosystem dynamics.

Andrographolide causes p53-independent HCC cell death through p62 accumulation and impaired DNA damage repair.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly lethal cancer characterized by dominant driver mutations, including p53. Consequently, there is an urgent need to search for novel therapeutic agents to treat HCC. Andrographolide (Andro), a clinically available anti-inflammatory phytochemical agent, has shown inhibitory effects against various types of cancer, including HCC. However, the underlying molecular mechanisms of its action remain poorly understood. PURPOSE: This study aims to investigate the molecular mechanisms by which p53 and p62 collectively affect Andro-induced HCC cell death, using both in vitro and in vivo models. METHODS: In vitro cellular experiments were conducted to examine the effects of Andro on cell viability and elucidate its mechanisms of action. In vivo xenograft experiments further validated the anti-cancer effects of Andro. RESULTS: Andro induced dose- and time-dependent HCC cell death while sparing normal HL-7702 hepatocytes. Furthermore, Andro caused DNA damage through the generation of reactive oxygen species (ROS), a critical event leading to cell death. Notably, HCC cells expressing p53 exhibited greater resistance to Andro-induced cell death compared to p53-deficient cells, likely due to the ability of p53 to induce G2/M cell cycle arrest. Additionally, Andro-induced p62 aggregation led to the proteasomal degradation of RAD51 and 53BP1, two key proteins involved in DNA damage repair. Consequently, silencing or knocking out p62 facilitated DNA damage repair and protected HCC cells. Importantly, disruption of either p53 or p62 did not affect the expression of the other protein. These findings were further supported by the observation that xenograft tumors formed by p62-knockout HCC cells displayed increased resistance to Andro treatment. CONCLUSION: This study elucidates the mechanistic basis of Andro-induced HCC cell death. It provides valuable insights for repurposing Andro for the treatment of HCC, regardless of the presence of functional p53.

Advances in the Application of Apoptotic Proteins and Alternative Splicing in Tumor Therapy: A Narrative Review.

An apoptosis-resistant state determined by apoptotic protein expression is commonly seen in the initiation, progression, and treatment failure stages of human cancer, and anti-tumor drugs targeting apoptotic proteins have been increasingly developed over the past three decades. However, the frequently alternative splicing of apoptotic proteins diminished the ability of targeting drugs to bind to apoptotic proteins and, consequently, limit the drug efficacy. Currently, accumulating evidence has demonstrated that many alternative splicing events have been associated to apoptosis resistance in different cancers. Therefore, the intervention targeting alternative splicing for regulating tumor cell apoptosis is expected to become a new strategy and new direction of antitumor therapy. Here, we present well established alternative splicing events that occur in different apoptosis-related genes and their modification by several approaches with cancer therapeutic purposes.

[Effects of transcutaneous electrical acupoint stimulation on the postoperative sleep quality and inflammatory factors in frail elderly patients].

OBJECTIVE: To observe the effects of transcutaneous acupoint stimulation (TEAS) on sleep quality and inflammatory factor in frail elderly patients undergoing laparoscopic colorectal cancer surgery. METHODS: A total of 100 frail elderly patients undergoing elective laparoscopic colorectal cancer surgery were randomly divided into an observation group and a control group, 50 cases in each one. Patients in the observation group received TEAS, 30 min before surgery until the end of surgery, at 18:00 on the day of surgery and on the 1st, 2nd and 3rd day after surgery (30 min each time). TEAS was delivered at bilateral Neiguan (PC 6), Shenmen (HT 7) and Hegu (LI 4). The disperse-dense wave of 2 Hz/100 Hz was selected, and the maximal stimulation intensity depended on patient's tolerance. The operation procedure in the control group was same as the observation group, but without electric stimulation exerted. The 1st day before surgery and on the 1st, 3rd and 7th day after surgery, the scores of Pittsburgh sleep quality index (PSQI) and Athens insomnia scale (AIS), as well as the serum levels of C reactive protein (CRP) and interleukin-6 (IL-6) were observed in the patients of two groups. At 24 h, 48 h and 72 h after surgery, the score of pain visual analogue scale (VAS) was recorded in the two groups, as well as the pressing times of analgesic pump and the usage of flurbiprofen axetil during analgesic stage. The occurrence of post operative adverse reactions was observed in the patients of two groups. RESULTS: On the 1st and 3rd day after surgery, except the usage of hypnotic drug scores, the scores of each item and the total scores of PSQI, as well as AIS scores were all increased in the two groups compared with those of 1 day before surgery (P<0.05); and the scores in the observation group were lower than those in the control group (P<0.05). On the 7th day after surgery, the scores of each item and the total scores of PSQI, and AIS scores were not different statistically in comparison between the two groups (P>0.05). On the 1st, 3rd and 7th day after surgery, serum levels of CRP and IL-6 were all increased in the patients of two groups when compared with those of 1 day before surgery (P<0.05), serum levels CRP and IL-6 in the patients of the observation group were lower than those of the control group (P<0.05). The VAS scores of 24 h, 48 h and 72 h after surgery, the pressing times of analgesic pump, the frequency and dosage of the remedies were not different statistically between the two groups (P>0.05). CONCLUSION: TEAS can effectively improve sleep quality and reduce inflammatory reaction in frail elderly patients undergoing laparoscopic colorectal cancer surgery.

Beneficial effect of electroacupuncture on the distribution of foreign substances in the brain of rats developing depression-like behavior.

We used low and high molecular weight fluorescence tracers to investigate the entry of foreign solutes into the brain parenchyma and their exit from it by the glymphatic system, during experimentally induced depressive-like behavior in rats. The tail suspension test (TST), as an acute stressor, is known to induce such a type of behavior, considered to model the human major depressive disorder (MDD). Electroacupuncture (EAP) relieves both depressive-like behavior in rodents and the symptoms of MDD in humans. Here we report that 180 min after the intracisternal injection of the low molecular weight tracer Fluorescein-5-Isothiocianate Conjugated Dextran (FITC-d3), a 15-min duration TST tended to increase the control fluorescence in the brain of rats. Both EAP and sham EAP decreased the fluorescence of FITC-d3 in comparison with the TST, but not the control value. In addition, EAP and sham EAP counteracted the effects of TST. The high molecular weight tracer Ovalbumin Alexa Fluor 555 Conjugate (OA-45) failed to enter the brain parenchyma and accumulated at more superficial sites; however, EAP or sham EAP modified the distribution of fluorescence under TST application in a similar manner as that observed during the use of FITC-d3. It is concluded that EAP is possibly a valid treatment to slow down the entry of foreign solutes into the brain; in view of the comparable effects of EAP on FITC-d3 and OA-45 distribution, EAP seems to act before FITC-d3 passes the astroglial aquaporin-4 water channels, which are a critical constituent of the glymphatic system.

Tailoring Adjuvant Chemotherapy to Biologic Response Following Neoadjuvant Chemotherapy Impacts Overall Survival in Pancreatic Cancer.

BACKGROUND: The role of postoperative chemotherapy in patients with resected pancreatic cancer who receive neoadjuvant treatment is unknown. Clinicians use changes in CA19-9 and histopathologic scores to assess treatment response. We sought to investigate if CA19-9 normalization in response to NAT can help guide the need for postoperative treatment. METHODS: Patients with elevated baseline CA19-9 (CA19-9 > 37U/mL) who received NAT followed by surgery between 2011 and 2019 were retrospectively reviewed. Treatment response was determined by CA19-9 normalization following NAT and histopathologic scoring. The role of postoperative chemotherapy was analyzed in light of CA19-9 normalization and histopathologic response. RESULTS: We identified and included 345 patients. Following NAT, CA19-9 normalization was observed in 125 patients (36.2%). CA19-9 normalization was associated with a favorable histopathologic response (41.6% vs 23.2%, p < 0.001) and a lower ypT (p < 0.001) and ypN stage (p = 0.003). Receipt of adjuvant chemotherapy was associated with improved overall survival in patients in whom CA19-9 did not normalize following NAT (26.8 vs 16.4 months, p = 0.008). In patients who received 5FU-based NAT and in whom CA19-9 did not normalize, receipt of 5FU-based adjuvant chemotherapy was associated with improved OS (p = 0.014). CONCLUSION: CA19-9 normalization in response to NAT was associated with favorable outcomes and can serve as a biomarker for treatment response. In patients where CA19-9 did not normalize, receipt of postoperative chemotherapy was associated with improved OS. These patients also benefited from additional 5FU-based postoperative chemotherapy following 5FU-based NAT.

Ratiometric fluorescent Si-FITC nanoprobe for immunoassay of SARS-CoV-2 nucleocapsid protein.

Coronavirus disease 2019 (COVID-19) highlights the importance of rapid and reliable diagnostic assays for the management of virus transmission. Here, we developed a one-pot hydrothermal method to prepare Si-FITC nanoparticles (NPs) for the fluorescent immunoassay of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein (N protein). The synthesis of Si-FITC NPs did not need post-modification, which addressed the issue of quantum yield reduction during the coupling reaction. Si-FITC NPs showed two distinct peaks, Si fluorescence at λ em = 385 nm and FITC fluorescence at λ em = 490 nm. In the presence of KMnO4, Si fluorescence was decreased and FITC fluorescence was enhanced. Briefly, in the presence of N protein, catalase (CAT)-linked secondary antibody/reporter antibody/N protein/capture antibody immunocomplexes were formed on microplates. Subsequently, hydrogen peroxide (H2O2) and Si-FITC NPs/KMnO4 were injected into the microplate together. The decomposition of H2O2 by CAT resulted in remaining of KMnO4, which changed the fluorescence intensity ratio of Si-FITC NPs. The fluorescence intensity ratio correlated significantly with the N protein concentration ranging from 0.02 to 50.00 ng/mL, and the detection limit was 0.003 ng/mL, which was more sensitive than the commercial ELISA kit with a detection limit of 0.057 ng/mL. The N protein concentration can be accurately determined in human serum. Furthermore, the COVID-19 and non-COVID-19 patients were distinguishable by this method. Therefore, the ratiometric fluorescent immunoassay can be used for SARS-CoV-2 infection diagnosis with a high sensitivity and selectivity. Electronic Supplementary Material: Supplementary material (characterization of Si-FITC NPs (FTIR, HRXPS); stability investigation of Si-FITC NPs (photostability, pH stability, anti-interference ability); stability investigation of free FITC (pH value, KMnO4); quenching mechanism of KMnO4 (UV-vis absorption spectra, fluorescence lifetime decay curves); reaction condition optimization of biotin-CAT with H2O2 (pH value, temperature, time); detection of N protein using commercial ELISA Kit; selectivity investigation of assays for SARS-CoV-2 N protein detection; determination results of SARS-CoV-2 N protein in human serum) is available in the online version of this article at 10.1007/s12274-022-5005-z.

Human growth hormone supplement promotes human lymphohematopoietic cell reconstitution in immunodeficient mice.

Aim: To investigate the potential of human growth hormone (hGH) to improve human hematopoietic reconstitution in humanized mice. Materials & methods: Immunodeficient mice were conditioned by total body irradiation and transplanted with human CD34+ fetal liver cells. Peripheral blood, spleen and bone marrow were harvested, and levels of human lymphohematopoietic cells were determined by flow cytometry. Results: Supplementation with hGH elevated human lymphohematopoietic chimerism by more than twofold. Treatment with hGH resulted in significantly increased reconstitution of human B cells and myeloid cells in lymphoid organs, enhanced human erythropoiesis in the bone morrow, and improved engraftment of human hematopoietic stem cells. Conclusion: hGH supplementation promotes human lymphohematopoietic reconstitution in humanized mice.

Humanized mice generated by human hematopoietic stem cell transplantation play crucial roles in biomedical investigations. One of the factors hindering the efficacy of their construction is the lack of or insufficient interaction of human cells to mouse cytokines and growth hormones (GHs) that are crucial for hematopoiesis and immune cell differentiation. In this study, we show that injection of human GH significantly improved human hematopoietic stem cell engraftment and function, as well as immune cell reconstitution in humanized mice. Our findings indicate that human cells may not efficiently respond to mouse GH, and generation of immunodeficient mice producing human GH may improve the efficacy of humanized mouse construction.

Relationship between serum parathyroid hormone levels and abdominal aortic calcification in patients starting hemodialysis who have never taken calcium tablets, calcitriol, or vitamin D analogs.

BACKGROUND: Vascular calcification (VC) and secondary hyperparathyroidism (SHPT) are important causes of the high incidence of cardiovascular events in chronic kidney disease (CKD) patients. The relationship between parathyroid hormone (PTH) and VC is very complex. The aim of this study was to determine the correlation between PTH levels and abdominal aortic calcification (AAC) in patients starting hemodialysis who had not received calcium tablets, calcium-containing phosphorus binders, calcitriol, or vitamin D analogs. METHODS: Seventy-one patients were included. Latero-lateral X-ray lumbar radiography, serum intact PTH (iPTH) levels, and predialysis biochemical parameters were obtained. The degree of AAC was evaluated according to the methods described previously by Kauppila et al. RESULTS: We found that there was a strong negative correlation between serum PTH and AAC (Spearman's rho -0.76, p < 0.001). Receiver operating characteristic (ROC) curve analysis showed that low serum PTH level could predict the presence and extent of AAC (area under the curve values were 0.9013 [p < 0.0001] and 0.780 [p = 0.0041], respectively). CONCLUSIONS: Our results indicate that serum PTH level is significantly negatively correlated with AAC within a certain concentration range in patients starting hemodialysis who had not received calcium tablets, calcium-containing phosphorus binders, calcitriol, or vitamin D analogs.

Selenium distribution in cultivated Argosols and Gleyosols of dry and paddy lands: A case study in Sanjiang Plain, Northeast China.

Distribution pattern of selenium (Se) fractions in soil could influence Se content in crops and thereby intake of Se in human body. In order to investigate the effects of soil types and farming conditions on Se distribution in small-scaled cultivated land developed under the same conditions of climate, topography and parent materials, two types of soils (i.e., Argosols and Gleyosols) from paddy and dry lands in the Sanjiang Plain of Northeast China were selected. Total Se (T-Se) content in Argosols was influenced by organic carbon (Org C) content and pH of bulk topsoil. In Gleyosols, it was mainly affected by Org C content in dry land and pH in paddy land, respectively. In rice root associated topsoil, organic matter associated Se (OM-Se) accounted for 70% of T-Se. Compared with pH (median 6.10) and OM weakly bound Se (OW-Se) (0.14 ± 0.04 mg kg-1) of Argosols, the higher pH (median 6.77) resulted in less OW-Se (0.10 ± 0.04 mg kg-1) of Gleyosols. Vertical distribution of Se in borehole cores within the depth of 0-900 cm was mainly affected by the soil type. Se accumulated mainly within 0-150 cm depth (horizon A, E and B) in Argosols and above 40 cm depth (horizon H), existing prominently as OM strongly bound Se (OS-Se), in Gleyosols. Within the depth of 0-150 cm, various Se fractions for both soils were probably controlled by reductive fixation and complexation of Org C; In the alkaline paddy land, DOM-complexed Se was the main composition of A-Se. The findings of this study could help in understanding the mechanisms of Se distribution and enrichment in soils developed under different formation processes and farming conditions.

Traditional soybean (Glycine max) breeding increases seed yield but reduces yield stability under non-phosphorus supply.

Traditional soybean (Glycine max L.) breeding has improved seed yield in high-input agricultural systems, under high nitrogen (N), phosphorus (P) and potassium (K) supply. The seed yield improvements under non-P supply and the seed protein and mineral content dilution by yield improvement were evaluated in 18 soybean cultivars released from 1995 to 2016 in south-east China. Soybean varieties were grown under rainfed conditions in the field under 0 and 35kgPha-1 in four sites: Dafang and Shiqian in the growing season of 2017 and Dafang and Puding in the 2018 season. The seed yield, seed protein content and nine seed nutrition concentration were examined. Soybean seed yield increased with the year of release at rates of 5.5-6.7gm-2 year-1 under 35kgPha-1 and 3.9-4.8gm-2 year-1 under non-P supply in the four experiments. The increase resulted from increases in the number of filled-pods and total seed number rather than from single seed weight and number of seeds per pod. Seed protein content and seed nutrition concentration has not changed with the year of release under 0 and 35kgPha-1 . Grain yield was positively correlated with the seed Fe concentration. The cultivar superiority of seed yield, seed P, Zn and Ca concentration was negatively correlated with their static stability coefficient. Traditional soybean breeding increased yield under both P and non-P supply, without affecting seed protein content and mineral concentrations. A trade-off between high seed yield and seed P, Zn and Ca concentration and their stability under different environments was shown.

Supplementation of Alhagi honey polysaccharides contributes to the improvement of the intestinal immunity regulating the structure of intestinal flora in mice.

Alhagi honey polysaccharides (AH), a main active component of Alhagi honey, are known to possess excellent pharmacological activities and have been widely used as dietary supplements in traditional Chinese medicine for thousands of years. This study is aimed to investigate the heath effect of AH on murine intestinal mucosal immune function and composition of the gut microbiome. ICR mice received daily intragastric administration of AH (three dosages, 200 mg kg-1, 400 mg kg-1, and 800 mg kg-1) or saline for 7 consecutive days. Results indicated an improvement in the intestinal barrier function through increases in secretory immunoglobulin A (sIgA) and ß-defensins. Simultaneously, AH also significantly stimulated IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α cytokine secretion as compared to the control samples. Moreover, hematoxylin and eosin staining showed that AH enhanced the number of intraepithelial lymphocytes (IELs) in the small intestine. An obvious increase in the ratio of IgA+ cells of AH-treatment samples in the lamina propria was also detected by immunohistochemical staining. In addition, the CD3+, CD4+ and CD8+ T-cell ratio in mesenteric lymph nodes and Peyer's patches in the AH-treatment was significantly higher than that in the control group. Furthermore, 16S rDNA gene sequencing was used to monitor the dynamic changes in the gut microbiota. The result revealed that AH significantly increased the indexes of Shannon and obviously decreased the indexes of Simpson, suggesting the enhancement of the diversity and richness of the intestinal microbiome. Moreover, AH modulated the gut microbiome via increasing the abundance of probiotics and decreasing the levels of pathogenic bacteria. In summary, these results indicated that AH could be used as a prebiotic to enhance murine intestinal mucosal immunity and to modulate the gut microbiome.

Herb-partitioned moxibustion regulated the miRNA expression profile in the thyroid tissues of rats with experimental autoimmune thyroiditi.

OBJECTIVE: To observe the effect of herb-partitioned moxibustion (HPM) on the miRNA expression profile of thyroid tissue in experimental autoimmune thyroiditis (EAT) rats. METHODS: Rats were randomly divided into normal control (NC) group, EAT model (EAT) group, HPM group and western medicine (Med) group. EAT model rats were prepared by a combined immunization with complete and incomplete Freund's adjuvant emulsified with porcine thyroglobulin and iodine. Rats in the HPM group were treated with HPM, while rats in the Med group were treated with levothyrocine (1 µg/2 mL) by gavage. HE staining was used to observe the pathological morphological changes of thyroid tissue, ELISAs was uaed to detect the serum concentrations of TGAb, TPOAb, FT3, FT4, TSH. We then performed high-throughput miRNA sequencing to analyse the miRNA expression profiles in the thyroid tissues, followed by a bioinformatics analysis. RT-qPCR was used to verify the identified differentially expressed miRNAs. RESULTS: HPM improved the thyroid tissue morphology and reduced serum TPOAb, TGAb, TSH concentration in EAT rats (P < 0.05), but with no obvious effect on FT3 and FT4 concentration. While the TSH, FT3 and FT4 concentration was significantly changed in the Med group (P < 0.01 or P < 0.05) compared with that of EAT group. Sequencing results showed that a total of 17 miRNAs were upregulated, and 4 were downregulated in the EAT rats, in which the expression levels of miR-346 and miR-331-5p were reversed by HPM. The target genes of the miRNAs that regulated by HPM were associated with a variety of immune factors and immune signals. RT-qPCR verification showed that the expression of miRNA-346 and miRNA-331-5p was consistent with the sequencing results. CONCLUSIONS: HPM could regulate the the expression of miRNA-346 and miRNA-331-5p, then act on their target genes to immune and inflammation-related pathways, which may be one of the mechanisms of HPM on EAT rats.