Triterpenoid saponins from Bupleurum marginatum and their anti-liver fibrotic activities.

A new triterpenoid saponin (1), along with five known compounds (2-6), was isolated from Bupleurum marginatum Wall. ex DC, of which compounds 2-4 were obtained for the first time from this plant. The structures were confirmed by the analysis of 1D, 2D NMR, and HR-ESIMS data, and comparison with previous spectral data. Anti-liver fibrotic activities of the isolates were determined as proliferation inhibition of LPS-induced activation of HSC-T6 in vitro.

Prevention of STAT3-related pathway in SK-N-SH cells by natural product astaxanthin.

PURPOSE: Neuroblastoma (NB) is the most common solid malignancy in children. Despite current intensive treatment, the long-term event-free survival rate is less than 50% in these patients. Thus, patients with NB urgently need more valid treatment strategies. Previous research has shown that STAT3 may be an effective target in high-risk NB patients. However, there are no effective inhibitors in clinical evaluation with low toxicity and few side effects. Astaxanthin is a safe and natural anticancer product. In this study, we investigated whether astaxanthin could exert antitumor effects in the SK-N-SH neuroblastoma cancer cell line. METHOD: MTT and colony formation assays were used to determine the effect of astaxanthin on the proliferation and colony formation of SK-N-SH cells. Flow cytometry assays were used to detect the apoptosis of SK-N-SH cells. The migration and invasion ability of SK-N-SH cells were detected by migration and invasion assays. Western blot and RT-PCR were used to detect the protein and mRNA levels. Animal experiments were carried out and cell apoptosis in tissues were assessed using a TUNEL assay. RESULT: We confirmed that astaxanthin repressed proliferation, clone formation ability, migration and invasion and induced apoptosis in SK-N-SH cells through the STAT3 pathway. Furthermore, the highest inhibitory effect was observed when astaxanthin was combined with si-STAT3. The reason for this may be that the combination of astaxanthin and si-STAT3 can lower STAT3 expression further than astaxanthin or si-STAT3 alone. CONCLUSION: Astaxanthin can exert anti-tumor effect on SK-N-SH cells. The inhibitory effect was the higher when astaxanthin was combined with si-STAT3.

Evaluation of Decontamination Potential of Wet Wipes Against Microbial Contamination of Chinese Spacecraft Materials.

Abstract There are many kinds of microorganisms that inhabit the environment of manned space stations. Wet wipes are a common tool used in space stations to clean and reduce microorganisms on surfaces. Here, we compared the performance of five types of wipes used by the Chinese Space Station (CSS) on orbit before 2021 in terms of microbial decontamination. In previous studies, we found that Bacillus sp. TJ-1-1 and Staphylococcus sp. HN-5 were the most abundant microorganisms in the assembly environment of the CSS. In this study, we used these two bacteria to build different microbial load models to represent the occurrence and non-occurrence of microbial outbreaks in the on-orbit CSS. The results show that the number of microorganisms that can be removed when wiping the surface with high microbial load by wet wipes was higher than that when wiping the surface with low microbial load. For on-orbit daily cleaning and keeping the microbial population within the regulation concentration range, it is suitable to use two pure water wipes per 100 cm2. When the number of microorganisms increases to a degree where astronauts can see the colonies with their naked eyes, the best way to eliminate the problem is to wipe them thoroughly and repeatedly with at least four quaternary ammonium-based wipes every 100 cm2.

Two new triterpenoid saponins from Bupleurum marginatum Wall. ex DC.

Two new triterpenoid saponins (1 and 2), together with two known saponins (3 and 4) were isolated from Bupleurum marginatum Wall. ex DC. Their structures were elucidated by the comprehensive spectroscopic analysis. Compounds 1 and 2 represented the rare example of an oleanane-type triterpenoid with two sugar moieties at C-3 and C-28. The cytotoxic activity of four compounds was evaluated against normal heptocell BRL-3A in vitro.

A New Player in Depression: MiRNAs as Modulators of Altered Synaptic Plasticity.

Depression is a psychiatric disorder that presents with a persistent depressed mood as the main clinical feature and is accompanied by cognitive impairment. Changes in neuroplasticity and neurogenesis greatly affect depression. Without genetic changes, epigenetic mechanisms have been shown to function by regulating gene expression during the body's adaptation to stress. Studies in recent years have shown that as important regulatory factors in epigenetic mechanisms, microRNAs (miRNAs) play important roles in the development and progression of depression through the regulation of protein expression. Herein, we review the mechanisms of miRNA-mediated neuroplasticity in depression and discus synaptic structural plasticity, synaptic functional plasticity, and neurogenesis. Furthermore, we found that miRNAs regulate neuroplasticity through several signalling pathways to affect cognitive functions. However, these pathways do not work independently. Therefore, we try to identify synergistic correlations between miRNAs and multiple signalling pathways to broaden the potential pathogenesis of depression. In addition, in the future, dual-function miRNAs (protection/injury) are promising candidate biomarkers for the diagnosis of depression, and their regulated genes can potentially be used as target genes for the treatment of depression.

Mannose inhibits the growth of prostate cancer through a mitochondrial mechanism.

The limited treatment options for advanced prostate cancer (PCa) lead to the urgent need to discover new anticancer drugs. Mannose, an isomer of glucose, has been reported to have an anticancer effect on various tumors. However, the anticancer effect of mannose in PCa remains unclear. In this study, we demonstrated that mannose inhibits the proliferation and promotes the apoptosis of PCa cells in vitro, and mannose was observed to have an anticancer effect in mice without harming their health. Accumulation of intracellular mannose simultaneously decreased the mitochondrial membrane potential, increased mitochondrial and cellular reactive oxygen species (ROS) levels, and reduced adenosine triphosphate (ATP) production in PCa cells. Mannose treatment of PCa cells induced changes in mitochondrial morphology, caused dysregulated expression of the fission protein, such as fission, mitochondrial 1 (FIS1), and enhanced the expression of proapoptotic factors, such as BCL2-associated X (Bax) and BCL2-antagonist/killer 1 (Bak). Furthermore, lower expression of mannose phosphate isomerase (MPI), the key enzyme in mannose metabolism, indicated poorer prognosis in PCa patients, and downregulation of MPI expression in PCa cells enhanced the anticancer effect of mannose. This study reveals the anticancer effect of mannose in PCa and its clinical significance in PCa patients.

Microbial degradation and community structure analysis of hydroxyl-terminated polybutadiene (HTPB).

Hydroxyl-terminated polybutadiene (HTPB) is a curing adhesive that is commonly used in the production of ammunition, and it emerged during the time of war. After entering the peaceful era, several countries around the globe have focused on the destruction of expired ammunition using safe and economical methods in terms of consumption of energy. Microorganisms exhibit a highly efficient and environment friendly degradation capability for variety of refractory substances. Therefore, in this study we screened five strains of microorganisms from five environmental soil samples for their ability to degrade HTPB. These microorganisms were identified as Microbacterium trichothecenolyticum, Microbacterium esteraromaticum, Arthrobacter pascens, Pseudonocardia carboxydivorans and Ochrobactrum anthropic based on 16S rRNA gene similarity index. We observed the uncorroded and corroded HTPB sample through scanning electron microscopy and observed the formation of lot of holes and gullies in HTPB after corrosion. An 18S rRNA gene clone library was constructed for HTPB-degrading fungi. Based on the results of library evaluation, it was found that the structure of the HTPB-degrading fungi community was relatively simple. A total of 54 positive clones were obtained. These clones represented some uncultured microorganisms that were closely related to Scytalidium lignicola, Pseudokahliella and Gonostomum strenuum. This study will help in the implementation of environment friendly degradation strategies for HTPB degradation.

Rapid identification and structural characterization of polyoxypregnane glycosides in Dregea sinensis by HPLC-MSn and HRMS.

By HPLC-MSn and HRMS analyses, the structures of 52 polyoxypregnane glycosides were rapidly inferred from Dregea sinensis Hemsl on the basis of their sodium-cationized molecules [M + Na]+ and predominant diagnostic ions resulting from the saccharic chain on C3 and the neutral loss of substituent on C11 and C12. Compounds 1 and 7 significantly inhibited LPS-stimulated splenocyte proliferation in vitro.[Formula: see text].

Survey and Evaluation of Spacecraft-Associated Aluminum-Degrading Microbes and Their Rapid Identification Methods.

Aluminum corrosion has become a major obstacle in spacecraft construction given that aluminum is used extensively throughout the construction process. Despite its many attributes in strength and durability, aluminum is susceptible to corrosion, in particular, corrosion due to microbial contamination. Scientists have encountered a number of problems with microbial aluminum corrosion within spacecraft components. Here, we summarize recent findings with regard to the phenomenon of microbiologically influenced corrosion (MIC) on space stations in the context of microbial strains isolated from the Mir space station (Mir) and the International Space Station (ISS). Given that strains found on spacecraft are of terrestrial origin, an understanding of the contribution of Al-corrosive microbes to corrosion and related risks to space travel and astronaut health is essential for implementation of prevention strategies. Accordingly, an efficient rapid identification method of microbes with the capability to degrade aluminum is proposed. In particular, onboard implementation of a matrix-assisted laser desorption/ionization-time of flight mass spectrometer (MALDI-TOF MS) is addressed. The use of a MALDI-TOF MS on board spacecraft will be crucial to future successes in space travel given that traditional methods of identifying corrosive species are far more time-consuming. Identification of microbes by way of a MALDI-TOF MS may also aid in the study of microbial corrosion and be a valuable asset for MIC prevention.

Evaluating Quantitative Measures of Microbial Contamination from China's Spacecraft Materials.

Different methods are used for the quantification of microbial load on spacecrafts. Here, we investigated a number of methodologies currently in use with the intent to identify the most accurate methods for the quantification of microbes on low-biomass metal surfaces such as those used in China's Space Station. In a previous study, we observed a high abundance of Bacillus sp. TJ 1-1 on interior surfaces of China's Space Station, and we therefore undertook this study in which we used a range of 102 to 109 cells/100 cm2 of this strain for setting different contamination levels. Four of the most common analytical approaches (contact plate, spread plate, quantitative PCR, and BacLight™) were used to quantify the number of viable microbial cells associated with the materials of China's Space Station. Results show that, for 102 cells/100 cm2, the contact plate method is the most convenient and reliable. For microbial contamination levels ≥103 cells/100 cm2 and a sampling area of 121 cm2, the BacLight method proved to be most reliable for the detection of live cells. Moreover, a sampling area of 121 cm2 was found to be the most suitable for analysis of metal surfaces for space station interiors, which are usually low in biomass. These results establish suitable sampling and processing methodologies for microbial enumeration of metal surfaces on China's Space Station.

The Impacts of Simulated Microgravity on Rat Brain Depended on Durations and Regions.

OBJECTIVE: To explore the dynamic impacts of simulated microgravity (SM) on different vital brain regions of rats. METHODS: Microgravity was simulated for 7 and 21 days, respectively, using the tail-suspension rat model. Histomorphology, oxidative stress, inflammatory cytokines and the expression of some key proteins were determined in hippocampus, cerebral cortex and striatum. RESULTS: 21-day SM decreased brain derived neurotrophic factor and induced neuron atrophy in the cerebral cortex. Strong oxidative stress was triggered at day 7 and the oxidative status returned to physiological level at day 21. Inflammatory cytokines were gradually suppressed and in striatum, the suppression was regulated partially through c-Jun/c-Fos. CONCLUSION: The results revealed that the significant impacts of SM on rat brain tissue depended on durations and regions, which might help to understand the health risk and to prevent brain damage for astronauts in space travel.

TRIB1 induces macrophages to M2 phenotype by inhibiting IKB-zeta in prostate cancer.

Immunotherapy has made great breakthroughs in the field of cancer. However, the immunotherapeutic effect of prostate cancer is unsatisfactory. We found that the expression of TRIB1 was significantly correlated with the infiltration of CD163+ macrophages in prostate cancer. This study focused on the effects of TRIB1 on macrophage polarization in the immune microenvironment of prostate cancer. RNA sequencing analysis demonstrated that TRIB1 has significant effects on the regulation of the nuclear factor (NF)-κB signaling pathway and downstream cytokines. Flow cytometry and enzyme-linked immunosorbent assay were used to examine THP-1 cells cultured in conditioned medium from prostate cancer cells overexpressing TRIB1 and showed that overexpression of TRIB1 promoted the secretion of CXCL2 and interleukin (IL)8 by PC3 cells, which increased the secretion of IL12 by THP-1 cells as well as the expression of CD163 on THP-1 cells. IKB-zeta, regulated by TRIB1, was expressed in PC3 cells but was barely detectable in DU145 cells. The reductions in CXCL2 and IL8 by the inhibition of TRIB1 were rescued by the deletion of IKB-zeta. Here we showed that TRIB1 promoted the secretion of cytokines from prostate cancer cells and induced the differentiation of monocytes/macrophages into M2 macrophages.

Microbiomes of China's Space Station During Assembly, Integration, and Test Operations.

Sufficient evidence indicates that orbiting space stations contain diverse microbial populations, which may threaten astronaut health and equipment reliability. Understanding the composition of microbial communities in space stations will facilitate further development of targeted biological safety prevention and maintenance practices. Therefore, this study systematically investigated the microbial community of China's Space Station (CSS). Air and surface samples from 46 sites on the CSS and Assembly Integration and Test (AIT) center were collected, from which 40 bacteria strains were isolated and identified. Most isolates were cold- and desiccation-resistant and adapted to oligotrophic conditions. Bacillus was the dominant bacterial genus detected by both cultivation-based and Illumina MiSeq amplicon sequencing methods. Microbial contamination on the CSS was correlated with encapsulation staff activities. Analysis by spread plate and qPCR revealed that the CSS surface contained 2.24 × 103-5.47 × 103 CFU/100 cm2 culturable bacteria and 9.32 × 105-5.64 × 106 16S rRNA gene copies/100cm2; BacLight™ analysis revealed that the viable/total bacterial cell ratio was 1.98-13.28%. This is the first study to provide important systematic insights into the microbiome of the CSS during assembly that describes the pre-launch microbial diversity of the space station. Our findings revealed the following. (1) Bacillus strains and staff activities should be considered major concerns for future biological safety. (2) Autotrophic and multi-resistant microbial communities were widespread in the AIT environment. Although harsh cleaning methods reduced the number of microorganisms, stress-resistant strains were not completely removed. (3) Sampling, storage and analytical methods for the space station were thoroughly optimized, and are expected to be applicable to low-biomass environments in general. Microbiology-related future works will follow up to comprehensively understand the changing characteristics of microbial communities in CSS.

Detection of Fungi from Low-Biomass Spacecraft Assembly Clean Room Aerosols.

Highly sensitive and rapid detection of airborne fungi in space stations is essential to ensure disease prevention and equipment safety. In this study, quantitative loop-mediated isothermal amplification (qLAMP) was used to detect fungi in the aerosol of the low-biomass environment of China's space station assembly clean room (CSSAC). A qLAMP primer set for detecting a wide range of aerosol fungi was developed by aligning 34 sequences of isolated fungal species and 17 space station aerosol-related fungal species. Optimization of sample pretreatment conditions of the LAMP reaction increased the quantitative results by 1.29-1.96 times. The results showed that our qLAMP system had high amplification specificity for fungi, with a quantifiable detection limit as low as 102. The detected fungal biomass in the aerosol of CSSAC was 9.59 × 102-2.20 × 105 28S rRNA gene copy numbers/m3. This qLAMP assay may therefore replace traditional colony-forming unit and quantitative PCR methods as an effective strategy for detecting fungi in space stations.

[Effect of androgen receptor on IgG expression, proliferation and migration of prostate cancer cells in vitro].

OBJECTIVE: To investigate the effect of androgen receptor (AR) on IgG protein expression and the proliferation and migration of prostate cancer cells. METHODS: Western blotting was used to detect the expression of AR protein and IgG in androgen-dependent prostate cancer LNCap cells and castration-resistant prostate cancer PC-3 cells. In AR-overexpressing cells (PC-3-AR cells) established by transfecting PC-3 with AR gene (pCDNA3.1) and LNCap cells with small interfering RNA-mediated AR silencing (LNCap-siAR cells) were analyzed for expressions of AR protein and IgG with Western blotting; the expression of IgG mRNA was detected by Q-PCR, and the cell proliferation and migration were assessed with MTT assay and wound healing assay, respectively. RESULTS: Compared with PC-3 cells, LNCap cells expressed a higher level of AR protein and a lower level of IgG (P<0.05). PC-3-AR cells showed attenuated proliferation and migration with a lowered expression of IgG (P<0.01), while LNCap-siAR cells showed enhanced proliferation and migration with increased expression of IgG (P<0.01). CONCLUSION: The expression of AR is inversely correlated with IgG and is associated with the proliferation and migration of prostate cancer cells in vitro.

Six new C-21 steroidal glycosides from Dregea sinensis Hemsl.

Six new C-21 steroidal glycosides (1-6) were separated from the root of Dregea sinensis Hemsl. and their structures were elucidated using extensive nuclear magnetic resonance, mass spectrometry, and infrared spectral analyses. Isolated compounds were evaluated for antitumor activity, which showed that compound 3 had moderate activity in Jurkat cells (IC50 19.54 ± 0.91 µM), and compounds 1-4 had significant effects against IL-2R and TNFR2 (IC50 1.518 ± 0.06 µM to 5.9 ± 0.07 µM).

C-21 steroidal glycosides from Dregea sinensis.

Two new C-21 steroidal glycosides, dregeosides D (1) and E (2), were isolated from the roots of Dregea sinensis. The structures of the isolated compounds were elucidated on the basis of 1D and 2D NMR spectra and HR-ESI-MS analysis. Finally, the inhibited effects of the isolated compounds on interleukin 2 receptor were evaluated by enzyme-linked immunosorbent assay.

Formation of a salsolinol-like compound, the neurotoxin, 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, in a cellular model of hyperglycemia and a rat model of diabetes.

There are statistical data indicating that diabetes is a risk factor for Parkinson's disease (PD). Methylglyoxal (MG), a biologically reactive byproduct of glucose metabolism, the levels of which have been shown to be increase in diabetes, reacts with dopamine to form 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (ADTIQ); this formation may provide further insight into the connection between PD and diabetes. In this study, we investigated the role of ADTIQ in these two diseases to determine in an aim to enhance our understanding of the link between PD and diabetes. To this end, a cell model of hyperglycemia and a rat model of diabetes were established. In the cell model of hyperglycemia, compared with the control group, the elevated glucose levels promoted free hydroxyl radical formation (p<0.01). An ADTIQ assay was successfully developed and ADTIQ levels were detected and quantified. The levels of its precursors, MG and dopamine (DA), were determined in both the cell model of hyperglycemia and the rat model of diabetes. The proteins related to glucose metabolism were also assayed. Compared with the control group, ADTIQ and MG levels were significantly elevated not only in the cell model of hyperglycemia, but also in the brains of rats with diabetes (p<0.01). Seven key enzymes from the glycolytic pathway were found to be significantly more abundant in the brains of rats with diabetes. Moreover, it was found that adenosine triphosphate (ATP) synthase and superoxide dismutase (SOD) expression levels were markedly decreased in the rats with diabetes compared with the control group. Therefore, ADTIQ expression levels were found to be elevated under hyperglycemic conditions. The results reported herein demonstrate that ADTIQ, which is derived from MG, the levels of which are increased in diabetes, may serve as a neurotoxin to dopaminergic neurons, eventually leading to PD.

Dragon's blood dropping pills have protective effects on focal cerebral ischemia rats model.

Dragon's blood is a bright red resin obtained from Dracaena cochinchinensis (Lour.) S.C.Chen (Yunnan, China). As a traditional Chinese medicinal herb, it has great traditional medicinal value and is used for wound healing and to stop bleeding. Its main biological activity comes from phenolic compounds. In this study, phenolic compounds were made into dropping pills and their protective effects were examined by establishing focal cerebral ischemia rats model used method of Middle Cerebral Artery Occlusion (MCAO), and by investigating indexes of neurological scores, infarct volume, cerebral index, cerebral water content and oxidation stress. Compared to model group, high, middle and low groups of Dragon's blood dropping pills could improve the neurological function significantly (p<0.01) and reduce cerebral infarct volume of focal cerebral ischemia rats remarkably (p<0.05-0.01). Meanwhile, each group could alleviate cerebral water content and cerebral index (p<0.05-0.01) and regulate oxidative stress of focal cerebral ischemia rats obviously (p<0.05-0.01). Activities of middle group corresponded with that treated with positive control drug. The results obtained here showed that Dragon's blood dropping pills had protective effects on focal cerebral ischemia rats.

Dragon's blood may have radioprotective effects in radiation-induced rat brain injury.

Dragon's blood is a bright red resin obtained from Dracaena cochinchinensis. It is a traditional medicinal that is used for wound healing and to stop bleeding. Its main biological activity appears to be from phenolic compounds found in Dragon's blood. In this study, the radioprotective effects of Dragon's blood were examined after whole brain irradiation of rats with either 100 MeV/u Carbon (12)C(6+) heavy ions or (60)Co γ-rays. The amounts of radiation-induced oxidative stress, inflammatory cytokines and apoptosis in irradiated rat brains were compared with and without Dragon's blood treatment. Compared to the "irradiation only" control group, the Dragon's blood treatment group significantly decreased malondialdehyde and hydrogen peroxide levels, and increased superoxide dismutase activity and glutathione levels induced by oxidative stress in radiation exposed rats (P < 0.05). Dragon's blood also significantly reduced radiation-induced inflammatory cytokines of tumor necrosis factor-α, interferon-γ and interleukin-6 levels (P < 0.05) and inhibited hippocampal neuronal apoptosis in (60)Co γ-ray irradiated rats. Furthermore, Dragon's blood significantly increased expression of brain-derived neurophic factor and inhibited the expression of pro-apoptotic caspase 3 (P < 0.05-0.01). Finally, Dragon's blood significantly inhibited expression of the AP-1 transcription factor family members c-fos and c-jun proteins (P < 0.05-0.01). The results obtained here suggest that Dragon's blood has radioprotective properties in rat brains after both heavy ions and (60)Co γ-ray exposure.