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.

Digestive system involvement of novel coronavirus infection: Prevention and control infection from a gastroenterology perspective.

An epidemic of an acute respiratory syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, now known as coronavirus disease 2019 (COVID-19), beginning in December 2019, has attracted an intense amount of attention worldwide. As the natural history and variety of clinical presentations of this disease unfolds, extrapulmonary symptoms of COVID-19 have emerged, especially in the digestive system. While the respiratory mode of transmission is well known and is probably the principal mode of transmission of this disease, a possibility of the fecal-oral route of transmission has also emerged in various case series and clinical scenarios. In this review article, we summarize four different aspects in published studies to date: (a) gastrointestinal manifestations of COVID-19; (b) microbiological and virological investigations; (c) the role of fecal-oral transmission; and (d) prevention and control of SARS-CoV-2 infection in the digestive endoscopy room. A timely understanding of the relationship between the disease and the digestive system and implementing effective preventive measures are of great importance for a favorable outcome of the disease and can help climnicians to mitigate further transmission by taking appropriate measures.

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.

Effect of Weightlessness on the 3D Structure Formation and Physiologic Function of Human Cancer Cells.

With the rapid development of modern medical technology and the deterioration of living environments, cancer, the most important disease that threatens human health, has attracted increasing concerns. Although remarkable achievements have been made in tumor research during the past several decades, a series of problems such as tumor metastasis and drug resistance still need to be solved. Recently, relevant physiological changes during space exploration have attracted much attention. Thus, space exploration might provide some inspiration for cancer research. Using on ground different methods in order to simulate microgravity, structure and function of cancer cells undergo many unique changes, such as cell aggregation to form 3D spheroids, cell-cycle inhibition, and changes in migration ability and apoptosis. Although numerous better experiments have been conducted on this subject, the results are not consistent. The reason might be that different methods for simulation have been used, including clinostats, random positioning machine (RPM) and rotating wall vessel (RWV) and so on. Therefore, we review the relevant research and try to explain novel mechanisms underlying tumor cell changes under weightlessness.

Novel treatment strategies for patients with HER2-positive breast cancer who do not benefit from current targeted therapy drugs.

Human epidermal growth factor receptor-2 positive breast cancer (HER2+ BC) is characterized by a high rate of metastasis and drug resistance. The advent of targeted therapy drugs greatly improves the prognosis of HER2+ BC patients. However, drug resistance or severe side effects have limited the application of targeted therapy drugs. To achieve more effective treatment, considerable research has concentrated on strategies to overcome drug resistance. Abemaciclib (CDK4/6 inhibitor), a new antibody-drug conjugate (ADC), src homology 2 (SH2) containing tyrosine phosphatase-1 (SHP-1) and fatty acid synthase (FASN) have been demonstrated to improve drug resistance. In addition, using an effective vector to accurately deliver drugs to tumors has shown good application prospects. Many studies have also found that natural anti-cancer substances produced effective results during in vitro and in vivo anti-HER2+ BC research. This review aimed to summarize the current status of potential clinical drugs that may benefit HER2+ BC patients in the future.

Laparoscopy-assisted versus open gastrectomy with D2 lymph node dissection for advanced gastric cancer: a meta-analysis.

A raising number of surgeons have chosen laparoscopy-assisted gastrectomy (LAG) as an alternative to open gastrectomy (OG) with D2 lymph node dissection for treatment of advanced gastric cancer (ADG). But no meta-analysis has been performed to evaluate the value of LAG versus OG with regard to safety and efficacy for treatment of ADG. A comprehensive literature research was performed in PubMed, Web of Science and Embase to identify studies that compared LAG and OG with D2 lymph node dissection for treatment of ADG. Data of interest were checked and subjected to meta-analysis with RevMan 5.1 software. 11 studies with 1904 patients (982 in LAG and 922 in OG) were enrolled. Pooled risk ratios (RR) and weighted mean difference (WMD) with 95% confidence intervals (CI) were appropriately derived from random-effects models or fixed-effects models. Compared with OG, LAG was associated with less blood loss (WMD = -144.47; P < 0.05), shorter time of first flatus time (WMD = -0.91; P < 0.05) and postoperative hospital stay (WMD = -3.27; P < 0.05), and lower morbidity (RR = 0.70; P < 0.05), but longer operation time (WMD = 41.78; P < 0.05). No significant differences were noted in terms of harvested lymph nodes (WMD = 1.85; P = 0.09), pathological N stage (χ(2) 3.97; P = 0.26), tumor size (WMD = -0.05; P = 0.81), mortality (RR 0.82; P = 0.76), cancer recurrence rate (RR 0.77; P = 0.18) and 3-year overall survival rate (RR 1.09; P = 0.18). Compared with OG, LAG with D2 lymph node dissection for ADG had the advantages of minimal invasion, faster recovery, and fewer complications, and it could achieve the same degree of radicality, harvested lymph nodes, short-term and long-term prognosis as OG, though the operation time was slightly longer.

[Intoxication induced by unsymmetrical dimethylhydrazine: characteristics and mechanism of its acute and chronic injuries].

OBJECTIVE: To investigate the characteristics and mechanism of the acute and chronic injuries induced by unsymmetrical dimethylhydrazine (UDMH). METHODS: A total of 128 male rats were randomly divided into four groups: UDMH intoxication acute response group and chronic response group, and corresponding control groups. UDMH was administrated through inhalation at the concentration of 8x10(-4)g/m(3) for 15 minutes. Animals of each group were sacrificed at 3, 6, 12, 24, 48 and 72 hours respectively after the intoxication. Pathologic changes and blood gas were examined. Chronic injuries and pathologic changes were also observed 1 year after the intoxication. RESULTS: Major pathological changes in the intoxication group were cerebral edema, degeneration and necrosis of neuron, enlargement and hemorrhage of capillary. Damages of different degree were found in liver, kidney, lung, heart, spleen, stomach, intestine, thymus, blood, bone marrow. Pallium ischemia was also found in the intoxicated rats 1 year after the intoxication, including ischemia damage of neuron in cerebral cortex, hemorrhage and focal liquefaction of thalamus and medulla conducting bind, dissociation, rupture, not uniform circuitry in conducting fibers. CONCLUSION: Our study reveals the basic pathological induced by intoxication of UDMH. The most severe stage of the injury appears 2-6 hours after intoxication. Long term investigation reveals pallium ischemia, thalamus hemorrhage and liquefaction in the medulla oblongata 1 year after the intoxication with UDMH. All the changes are significant.

[Characteristics of acute and chronic intoxication induced by rocket propellant nitrogen tetroxide].

OBJECTIVE: To investigate the characteristics of acute and chronic injuries of the nitrogen tetroxide, a kind of propellant of rocket. METHOD: 128 male rats were divided randomly into 4 groups: acute control group (56), acute nitrogen tetroxide intoxication group (56), long-term response group (8). The animals were killed sequentially at 3, 6, 12, 24, 48 and 72 h. Nitrogen tetroxide was administrated through inhalation at the concentration of 81 mg/m3 for 15 min. Chronic injuries and pathologic changes were also observed one year after the intoxication. RESULT: Pulmonary edema was the main pathological changes after intoxication, complicated with partial haemorrhage. Data acquired from long-term observations showed 75% pulmonary fibrosis and one case of adenocarcinoma of lung. CONCLUSION: The first 2 to 6 h after intoxication is the most severe stage of the injury. During the long-term observation, we find that intoxication with nitrogen tetroxide can induce pulmonary fibrosis and adenocarcinoma.

Changes of proton transportation across the inner mitochondrial membrane and H(+)-ATPase in endotoxic shock rats.

OBJECTIVE: To investigate the changes of proton transportation across the inner mitochondrial membrane (IMM) and H(+)-ATPase of hepatocytes in endotoxic shock rats. METHODS: Endotoxin from E. Coil of 5.0 mg/kg or saline of 1 ml/kg was injected into the femoral vein. The rats were sacrificed pre-injection and 1, 3, 5, 8 hours after injection, and plasma and liver tissue samples were collected respectively. The liver tissue samples were used for preparation of mitochondria and submitochondrial particles (SMPs). The proton-translocation of SMPs and H(+)-ATPase, phospholipase A(2) (PLA(2)) activities and malondialdehyde (MDA) content, membrane fluidities of different level of mitochondria membrane and plasma MDA content were assayed. RESULTS: (1) Five hours after E. Coli. O111B4 injection, the maximum fluorescence quenching ACMA after adding ATP, nicotinamide adenin dinucleoacid hydrogen (NADH), and the succinate were significantly decreased (P<0.05). The time of maximum fluorescent quenching and the half time of fluorescent quenching were significantly prolonged (P<0.01), especially when NADH was used as a substrate. (2) The mitochondrial H(+)-ATPase activity was significantly increased at early stage of endotoxic shock (P<0.05), and significantly decreased at late stage of endotoxic shock (P<0.01). (3) The mitochondrial membrane bound PLA(2) activity, plasmal and mitochondrial MDA content were significantly increased and succinate dehydrogenase (SDH) activity of mitochondria decreased markedly in endotoxic shock rats (P<0.05). (4) The mitochondrial membrane fluidity of different lipid regions was decreased, especially in the head of phospholipid. CONCLUSIONS: Proton transportation across IMM and mitochondrial H(+)-ATPase activity are significantly decreased in endotoxic shock.