Simulated microgravity altered the proliferation, apoptosis, and extracellular matrix formation of L929 fibroblasts and the transforming growth factor-ß1/Smad3 signaling pathway.

Exposure to microgravity can adversely affect the fitness of astronauts. The integrity of the skin plays a crucial role in protecting against mechanical forces and infections, fluid imbalance, and thermal dysregulation. In brief, the skin wound may cause unknown challenges to the implementation of space missions. Wound healing is a physiological process that relies on the synergistic action of inflammatory cells, extracellular matrix (ECM), and various growth factors to maintain the integrity of skin after trauma. Fibroblasts are present almost throughout the entire process of wound repair, especially in the scar formation at the endpoint of wound healing. However, there is limited knowledge about the extent to which fibroblasts are affected by the lack of gravity during wound healing. In this study, we utilized the rotary cell culture system, a ground-based facility that mimics the weightless condition, to study the alterations of L929 fibroblast cells under simulated microgravity (SMG). Our results demonstrated that the SM condition exerted negative influences on the proliferation and ECM formation of the L929 fibroblast. Whereas, the apoptosis of fibroblast was significantly upregulated upon exposure to SMG conditions. Moreover, the transforming growth factor-ß1/Smad3 (TGF-ß1/smad3) signaling pathway of L929 fibroblast related to wound repair was also altered significantly under a weightless environment. Overall, our study provided evidence that fibroblasts are strongly sensitive to SMG and elucidated the potential value of the TGF-ß1/Smad3 signaling pathway modulating wound healing in the future practice of space medicine.

Autophagy in hepatic macrophages can be regulator and potential therapeutic target of liver diseases: A review.

Hepatic macrophages are a complex population of cells that play an important role in the normal functioning of the liver and in liver diseases. Autophagy, as a maintainer of cellular homeostasis, is closely connected to many liver diseases. And its roles are not always beneficial, but manifesting as a double-edged sword. The polarization of macrophages and the activation of inflammasomes are mediated by intracellular and extracellular signals, respectively, and are important ways for macrophages to take part in a variety of liver diseases. More attention should be paid to autophagy of hepatic macrophages in liver diseases. In this review, we focus on the regulatory role of hepatic macrophages' autophagy in a variety of liver diseases; especially on the upstream regulator of polarization and inflammasomes activation of the hepatic macrophages. We believe that the autophagy of hepatic macrophages can become a potential therapeutic target for management of liver diseases.

Proteomic analysis of the effects of simulated microgravity in human gastric mucosal cells.

Microgravity is an ecological factor that affects the environment of the body. In this study, quantitative isobaric labeling (tandem mass tag) method was used to study the changes in human gastric mucosal cells under simulated microgravity for the first time. Comparative proteomic analysis identified 394 (202 upregulated and 192 downregulated) and 542 (286 upregulated and 256 downregulated) proteins differentially regulated by simulated microgravity after 3 and 7 days, respectively. Then the identified proteins were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses for further exploration. The results of the analysis showed that the ribosomes of gastric mucosal cells were significantly impacted after exposure to simulated microgravity for 3 days, and the cells appeared to be in a state of stress and inflammation. Exposure to simulated microgravity for 7 days significantly affected the mitochondria of the cells, oxidative stress became more evident, while inflammation and weakened connections were observed in the cells. The results of this study highlighted the temporal response trend of gastric mucosal cells to the stressor of microgravity at the two time points of 3 and 7 days. These findings will provide insights into the development of methods to protect the gastric mucosa during space flight.

Autophagy in Gastric Mucosa: The Dual Role and Potential Therapeutic Target.

The incidence of stomach diseases is very high, which has a significant impact on human health. Damaged gastric mucosa is more vulnerable to injury, leading to bleeding and perforation, which eventually aggravates the primary disease. Therefore, the protection of gastric mucosa is crucial. However, existing drugs that protect gastric mucosa can cause nonnegligible side effects, such as hepatic inflammation, nephritis, hypoacidity, impotence, osteoporotic bone fracture, and hypergastrinemia. Autophagy, as a major intracellular lysosome-dependent degradation process, plays a key role in maintaining intracellular homeostasis and resisting environmental pressure, which may be a potential therapeutic target for protecting gastric mucosa. Recent studies have demonstrated that autophagy played a dual role when gastric mucosa exposed to biological and chemical factors. More indepth studies are needed on the protective effect of autophagy in gastric mucosa. In this review, we focus on the mechanisms and the dual role of various biological and chemical factors regulating autophagy, such as Helicobacter pylori, virus, and nonsteroidal anti-inflammatory drugs. And we summarize the pathophysiological properties and pharmacological strategies for the protection of gastric mucosa through autophagy.

Correction to: Simulated microgravity significantly altered metabolism in epidermal stem cells.

The affiliation given for Yan Cui in this article is not correct. The following is the correction affiliation.

Effect of simulated microgravity on metabolism of HGC-27 gastric cancer cells.

The understanding into the pathogenesis and treatment of gastric cancer has improved in recent years; however, a number of limitations have delayed the development of effective treatment. Cancer cells can undergo glycolysis and inhibit oxidative phosphorylation in the presence of oxygen (Warburg effect). Previous studies have demonstrated that a rotary cell culture system (RCCS) can induce glycolytic metabolism. In addition, the potential of regulating cancer cells by targeting their metabolites has led to the rapid development of metabolomics. In the present study, human HGC-27 gastric cancer cells were cultured in a RCCS bioreactor, simulating weightlessness. Subsequently, liquid chromatography-mass spectrometry was used to examine the effects of simulated microgravity (SMG) on the metabolism of HGC-27 cells. A total of 67 differentially regulated metabolites were identified, including upregulated and downregulated metabolites. Compared with the normal gravity group, phosphatidyl ethanolamine, phosphatidyl choline, arachidonic acid and sphinganine were significantly upregulated in SMG conditions, whereas sphingomyelin, phosphatidyl serine, phosphatidic acid, L-proline, creatine, pantothenic acid, oxidized glutathione, adenosine diphosphate and adenosine triphosphate were significantly downregulated. The Human Metabolome Database compound analysis revealed that lipids and lipid-like metabolites were primarily affected in an SMG environment in the present study. Overall, the findings of the present study may aid our understanding of gastric cancer by identifying the underlying mechanisms of metabolism of the disease under SMG.

Simulated microgravity significantly altered metabolism in epidermal stem cells.

Simulated microgravity can significantly affect various cell types and multiple systems of the human body, such as cardiovascular system, skeletal muscle system, and immune system, and is known to cause anemia and loss of electrolyte and fluids. Epidermal stem cells (EpSCs) were cultured in a rotary cell culture system (RCCS) bioreactor to simulate microgravity. The metabolites of EpSCs were identified by liquid chromatography-mass spectrometry (LC-MS). Compared with normal gravity (NG) group, a total of 57 different metabolites of EpSCs were identified (P < 0.05, VIP > 1), including lipids and lipid-like molecules (51 molecules), amino acids (5 molecules), nucleosides, nucleotides, and analogues (1 molecule). According to the partial least squares discriminant analysis (PLS-DA) score plot, a VIP > 1 and P < 0.05 were obtained for the 57 different metabolites, of which 23 molecules were significantly downregulated and 34 were significantly upregulated in simulated microgravity (SMG) group. These results showed that SMG has a significant impact on different pathways, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that multiple pathways were involved, mainly the amino acid metabolism pathway, lipid metabolism pathway, membrane transport pathway, and cell growth and death pathways. Thus, the metabolic profile of EpSCs was changed under SMG. Exploring the metabolic profile of EpSCs would be helpful to further understand the growth characteristics of EpSCs under SMG, which will provide a new approach to explore the metabolomics mechanism of stress injury and repair trauma under SMG.

The effects of microgravity on the digestive system and the new insights it brings to the life sciences.

BACKGROUND: Weightlessness is a component of the complex space environment. It exerts adverse effects on the human body, and may pose unknown challenges to the implementation of space missions. The regular function of the digestive system is an important checkpoint for astronauts to conduct missions. Simulated microgravity can recreate the changes experienced by the human body in a weightless environment in space to a certain extent, providing technical support for the exploration of its mechanism and a practical method for other scientific research. METHODS AND MATERIALS: In the present study, we reviewed and discussed the latest research on the effects of weightlessness or simulated microgravity on the digestive system, as well as the current challenges and future expectations for progress in medical science and further space exploration. RESULTS: A series of studies have investigated the effects of weightlessness on the human digestive system. On one hand, weightlessness and the changing space environment may exert certain adverse effects on the human body. Studies based on cells or animals have demonstrated the complex effects on the human digestive system in response to weightlessness. On the other hand, a microgravity environment also facilitates the ideation of novel concepts for research in the domain of life science. CONCLUSION: The effects of weightlessness on the digestive system are considerably complicated. The emergence of methods that help simulate a weightless environment provides a more convenient alternative for assessing the impact and the mechanism underlying the effect of weightlessness on the human body. In addition, the simulated microgravity environment facilitates the ideation of novel concepts for application in regenerative medicine and other fields of life science.

Contrast-enhanced computed tomography findings of a huge perianal epidermoid cyst: A case report.

BACKGROUND: Epidermoid cysts can be found at any location in the human body. However, perianal epidermoid cysts are extremely rare and only a few cases have been reported. As far as we know, there is no special literature on the value of contrast-enhanced computed tomography (CT) for the diagnosis of perianal epidermoid cysts. CASE SUMMARY: A 60-year-old male patient presented to the department of general surgery of PLA Strategic Support Force Characteristic Medical Center with the chief complaint of a mass in the perianal region gradually expanding for more than 30 years and perianal discomfort upon sitting for a preceding period of 2 mo. Physical examination revealed a painless mass in the left perianal region. Contrast-enhanced CT was used for preoperative diagnosis. The patient was treated by total mass excision under epidural anesthesia. Postoperative pathological examination revealed the presence of a perianal epidermoid cyst. The patient showed a satisfactory recovery during the 6-month follow-up period. CONCLUSION: Contrast-enhanced CT may be a beneficial, useful, and convenient approach for assistance for preoperative diagnosis and surgical decision-making for patients with perianal epidermoid cysts.

[Assessment value of preoperative neutrophil-lymphocyte ratio for the prognosis of patients with colorectal cancer after radical operation].

OBJECTIVE: To assess the value of preoperative neutrophil-lymphocyte ratio (NLR) for prognosis in patients with colorectal cancer after radical operation. METHODS: Clinical data of 140 patients with colorectal cancer undergoing radical operation in the Department of General Surgery of General Hospital of PLA from July 2005 to July 2011 were analyzed retrospectively. According to preoperative NLR, patients were divided into the low NLR group (NLR<5, n=105) and the high NLR group (NLR≥5, n=35). The overall 5-year survival rates of two groups were compared and the independent risk factors were examined by univariate analysis and Cox model. RESULTS: The overall 5-year survival rates of the low and high NLR groups were 74.8% and 54.7% respectively with significant difference (P=0.03). Univariate analysis revealed depth of tumor, lymph nodes metastasis, TMN stage and NLR were associated with survival (P<0.05, P<0.01). Cox model showed that NLR was independent risk factor of prognosis (RR=1.068, 95%CI:1.009-1.129, P=0.02). CONCLUSION: Preoperative NLR≥5 predicts poorer prognosis of colorectal cancer patients.

[Analysis of treatment and prognosis in 34 patients with anorectal malignant melanoma].

OBJECTIVE: To explore the prognostic factors of anorectal malignant melanoma (ARMM). METHODS: Medical records and follow-up data of 34 patients with ARMM treated in the Chinese PLA General Hospital from March 1993 to November 2011 were analyzed retrospectively. RESULTS: There were 26 abdominoperineal resections(APR) and 8 wide local excisions (WLE). Twenty patients underwent postoperative adjuvant therapy, including chemotherapy in 14 cases, radiotherapy in 2 cases, traditional Chinese medicine therapy in 4 cases and immunotherapy in 16 cases. Postoperative follow-up was carried out in all the patients and the mean follow-up period was 27 months. The 1-, 3- and 5-year overall survival rates were 76.3%, 39.6% and 20.6% respectively, while the 1-, 3- and 5-year disease-free survival rates were 60.6%, 30.8% and 12.8% respectively. APR and postoperative immunotherapy could significantly reduce the local recurrence rate. According to the Kaplan-Meier method, gross type of tumor, mural involvement, lymph metastasis, and clinical staging had significant effects on overall survival, while lymph metastasis and postoperative immunotherapy on disease-free survival. Cox proportional hazards model indicated that the clinical staging and postoperative immunotherapy were significant predictive factors. CONCLUSIONS: Early diagnosis and correct choice of surgical method are the keys to the treatment. Postoperative immunotherapy can prolong disease-free survival.

New class of competitive inhibitor of bacterial histidine kinases.

Bacterial histidine kinases have been proposed as targets for the discovery of new antibiotics, yet few specific inhibitors of bacterial histidine kinases have been reported. We report here a novel thienopyridine (TEP) compound that inhibits bacterial histidine kinases competitively with respect to ATP but does not comparably inhibit mammalian serine/threonine kinases. Although it partitions into membranes and does not inhibit the growth of bacterial or mammalian cells, TEP could serve as a starting compound for a new class of histidine kinase inhibitors with antibacterial activity.