Thiamine-modified metabolic reprogramming of human pluripotent stem cell-derived cardiomyocyte under space microgravity.

During spaceflight, the cardiovascular system undergoes remarkable adaptation to microgravity and faces the risk of cardiac remodeling. Therefore, the effects and mechanisms of microgravity on cardiac morphology, physiology, metabolism, and cellular biology need to be further investigated. Since China started constructing the China Space Station (CSS) in 2021, we have taken advantage of the Shenzhou-13 capsule to send human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) to the Tianhe core module of the CSS. In this study, hPSC-CMs subjected to space microgravity showed decreased beating rate and abnormal intracellular calcium cycling. Metabolomic and transcriptomic analyses revealed a battery of metabolic remodeling of hPSC-CMs in spaceflight, especially thiamine metabolism. The microgravity condition blocked the thiamine intake in hPSC-CMs. The decline of thiamine utilization under microgravity or by its antagonistic analog amprolium affected the process of the tricarboxylic acid cycle. It decreased ATP production, which led to cytoskeletal remodeling and calcium homeostasis imbalance in hPSC-CMs. More importantly, in vitro and in vivo studies suggest that thiamine supplementation could reverse the adaptive changes induced by simulated microgravity. This study represents the first astrobiological study on the China Space Station and lays a solid foundation for further aerospace biomedical research. These data indicate that intervention of thiamine-modified metabolic reprogramming in human cardiomyocytes during spaceflight might be a feasible countermeasure against microgravity.

Vaginal microbiota: Potential targets for vulvovaginal candidiasis infection.

Vulvovaginal candidiasis (VVC) is the second most common cause of vaginal infection globally after bacterial vaginosis (BV) and associated with adverse reproductive and obstetric outcomes, including preterm delivery, sexually transmitted infections and pelvic inflammatory disease. Although effective control of VVC is achievable with the use of traditional treatment strategies (i.e., antifungals), the possibility of drug intolerance, treatment failure and recurrence, as well as the appearance of antifungal-resistant Candida species remain critical challenges. Therefore, alternative therapeutic strategies against VVC are urgently required. In recent years, an improved understanding of the dysbiotic vaginal microbiota (VMB) during VVC has prompted the consideration of administering -biotics to restore the balance of the VMB within the context of VVC prevention and treatment. Here, we aim to summarize the current evidence of the anti-Candida effects of probiotics, postbiotics and synbiotics and their potential use as an alternative/complementary therapy against VVC. Additionally, this review discusses advantages and challenges associated with the application of -biotics in VVC to provide guidance for their later use. We also review new developments in VVC therapy, i.e., vaginal microbiota transplantation (VMT) as an emerging live biotherapeutic therapy against VVC and discuss existing shortcomings associated with this nascent field, expecting to stimulate further investigations for introduction of new therapies against VVC.

Vitamin K3 Suppresses Pyroptosis in THP-1 Cells through Inhibition of NF-κB and JNK Signaling Pathways.

Vitamin K, a necessary nutritional supplement for human, has been found to exhibit anti-inflammatory activity. In the present study, we investigated the effects of vitamin K family on lipopolysaccharide (LPS) plus nigericin induced pyroptosis and explored the underlying mechanism of its action in THP-1 monocytes. Results showed that vitamin K3 treatment significantly suppressed THP-1 pyroptosis, but not vitamin K1 or K2, as evidenced by increased cell viability, reduced cellular lactate dehydrogenase (LDH) release and improved cell morphology. Vitamin K3 inhibited NLRP3 expression, caspase-1 activation, GSDMD cleavage and interleukin (IL)-1ß secretion in pyrophoric THP-1 cells. In addition, vitamin K3 inhibited the pro-inflammatory signaling pathways including nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK). Vitamin K3 treatment also attenuated tissue damage and reduced serum LDH, IL-1ß and IL-6 levels in LPS-induced systemic inflammation of mice. The reduced myeloperoxidase (MPO) activityand F4/80 expression indicated that vitamin K3 effectively reduced the infiltration of neutrophils and macrophages. Moreover, NLRP3 expression in monocytes/macrophages were also decreased in vitamin K3-treatedmice after LPS challenge. These findings suggest that vitamin K3 potently alleviates systemic inflammation and organ injury via inhibition of pyroptosis in monocytes and may serve as a novel therapeutic strategy for patients with inflammatory diseases.

Effect of Predictive Nursing Combined with Early Drinking Water Therapy on Patients with Urinary Retention after Vaginal Delivery.

The aim of this study is to analyze the effect of predictive nursing combined with early drinking water therapy on patients with urinary retention after vaginal delivery. A total of 600 women who gave birth in our hospital from July 2019 to July 2020 were selected as the research objects. A double-blind method was adopted to divide them into a control group and observation group, 300 cases in each group. In the control group, routine nursing was given. In the observation group, (1) predictive nursing measures were used before surgery. (2) The postoperative observation group used early drinking water therapy; the incidence of urinary retention, the effective rate of urination, postpartum haemorrhage, and the treatment of urinary retention were compared between the two groups. In the observation group, the number of urinary retention was 17, and the incidence of urinary retention was 5.67%. The urination efficiency of the observation group was 98.33%; the urination efficiency of the control group was 86.33%; comparison results showed that P < 0.05. The 24 h postpartum haemorrhage of the observation group was 1.33%; the 24 h postpartum haemorrhage of the control group was 2.66%. Uroschesis therapy was performed in 17 patients in the observation group and 44 patients in the control group.. The observation group had an 88.24 percent treatment rate, while the control group had a 72.73 percent treatment rate. P < 0.05 indicated that the difference was statistically significant.

Seven new chemical constituents from the underground parts of Eupatorium chinense.

Three new sesquiterpenoids (1-3) and four new benzofuran dimers (+)-4 and (-)-4, (+)-5 and (-)-5, and four known benzofuran dimers (+)-6 and (-)-6, (+)-7 and (-)-7 were isolated from the underground parts of Eupatorium chinense. The enantiomers of racemates (±)-4 ~ (±)-7 were separated by chiral HPLC columns, and their absolute configurations were determined by circular dichroism experiments. The structures of all new compounds were elucidated on the basis of their NMR, and MS data as well as by comparison with literature values. The all of the isolated compounds were tested in vitro for their cytotoxic activities against the Caski, MDA-MB-231 and HepG2 cancer cell lines.

[Effects of moxibustion on the structure and function of blood brain barrier in Alzheimer's disease model rats].

OBJECTIVE: To investigate the effects of moxibustion on the structure and function of blood-brain barrier in Alzheimer's disease (AD) model rats. METHODS: Forty-eight SD rats were randomly divided into 4 groups: normal control group, sham operation group, model group, moxibustion group. Model group and moxibustion group rats were injected with aggregated Aß25-35 by bilateral hippocampus. In the rat model, the sham-operated group was injected with the same amount of normal saline in the bilateral hippocampus, and the normal group was not treated. After successful modeling, the moxibustion treatment was given at 2～3 cm above the Baihui, Shenshu and Yintang points of the moxibustion group rats, each time for 10 min, once a day, continuous treatment for 21 d. The Morris water maze test was used to evaluate the learning and memory ability of rats in each group. The Evans blue method was used to detect the permeability of blood-brain barrier. The ultrastructure of blood-brain barrier was observed under electron microscope. The matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) positive cells in hippocampus were detected by immunohistochemistry. RESULTS: Compared with the sham operation group, the escape latency was significantly increased (P＜0.01), and the space exploration time was decreased (P＜0.01), the learning and memory function in model group was impaired seriously, the Evans blue content in the brain was increased significantly (P＜0.01), the perivascular edema became larger, and the blood-brain barrier structure function was impaired. At the same time, the positive expressions of MMP-2 and MMP-9 in hippocampus were increased significantly (P＜0.01). Compared with model group, the learning and memory ability in moxibustion group rats was enhanced (P＜ 0.05), the content of Evans blue in the brain was decreased (P＜0.05), the degree of perivascular edema was reduced, and the damage of blood-brain barrier was improved. Positive expressions of MMP-2 and MMP-9 in hippocampus were decreased (P＜0.05 or P＜ 0.01). CONCLUSION: Moxibustion can decrease the expressions of MMP-2 and MMP-9, and reduce the damage of the structure and function of blood-brain barrier, thereby improving the learning and memory ability of AD model rats, and exerting therapeutic effects.

Xanthone glycosides from Swertia bimaculata with α-glucosidase inhibitory activity.

Seven new xanthone glycosides (1-7) were isolated from the n-butanol extract of Swertia bimaculata, together with six known compounds (8-13). Their structures were elucidated on the basis of extensive spectroscopic analyses (1D- and 2D-NMR, HRESIMS, UV, and IR) and comparison with data reported in the literature. All the compounds were evaluated for their α-glucosidase inhibitory activities in vitro, and compounds 3, 4, and 7 exhibited significant activities to inhibit α-glucosidase. Meanwhile the effects of different substitutions on the α-glucosidase inhibitory activity of xanthone glycosides from S. bimaculata are also discussed.

[Study on Quality Standard for Panax japonicus Rhizome].

OBJECTIVE: To establish a quality standard for Panax japonicus rhizome. METHODS: Ginsenoside Ro and Chikusetsusaponin IVa were used as reference substances in the TLC identification and HPLC method. Additionally, acid insoluble ash and moisture were determined according to the procedures recorded in the Appendix of Chinese Pharmacopeia (2010 edition). RESULTS: The TLC identification with GF, showed a good resolution with clear spots and its optimum developer was the underlayer of chloroform-methanol-formic acid-water = 4.5:1.5: 0.1:0.3. The content of Ginsenoside Ro and Chikusetsusaponin N a were determined by HPLC. The mixture of acetonitrile and water (0.15% phosphate) with gradient elution as the mobile phase was used at a flow rate of 1.0 mL/min, the detection wavelength at 203 nm and the column temperature at 40 °C. The calibration curve was linear in the range of 31.25-2,000 g/mL for Ginsenoside Ro and Chikusetsusaponin IVa (r = 0.9999, respectively). The average recovery was 101.19% and 102.50%, and RSD was 1.59% and 1.80% respectively. The content of Ginsenoside Ro and Chikusetsusaponin IVa was no less than 1.5% respectively. An average content of moisture was 7.36% and acid insoluble ash was 0.84%. CONCLUSION: These methods are producible, sensitive and simple, which can be used to control the quality of Panax japonicus rhizome.

Holotransferrin enhances selective anticancer activity of artemisinin against human hepatocellular carcinoma cells.

Artemisinin, also termed qinghaosu, is extracted from the traditional Chinese medicine artemesia annua L. (the blue-green herb) in the early 1970s, which has been confirmed for effectively treating malaria. Additionally, emerging data prove that artemisinin exhibits anti-cancer effects against many types of cancers such as leukemia, melanoma, etc. Artemisinin becomes cytotoxic in the presence of ferrous iron. Since iron influx is high in cancer cells, artemisinin and its analogs selectively kill cancer cells with increased intracellular iron concentrations. This study is aimed to investigate the selective inhibitory effects of artemisinin on SMMC-7721 cells in vitro and determine the effect of holotransferrin, which increases the concentration of ferrous iron in cancer cells, combined with artemisinin on the anticancer activity. MTT assay was used for assessing the proliferation of SMMC-7721 cells treated with artemisinin. The induction of apoptosis and inhibition of colony formation in SMMC-7721 cells treated with artemisinin were determined by TdT-mediated dUTP nick end labeling (TUNEL) and colony formation assay, respectively. The results showed that artemisinin at various concentrations significantly inhibited growth, colony formation and cell viability of SMMC-7721 cells (P<0.05), likely due to induction of apoptosis of SMMC-7721 cells. Of interest, it was found that incubation of artemisinin combined with holotransferrin sensitized the growth inhibitory effect of artemisinin on SMMC-7721 cells (P<0.01). Our data suggest that treatment with artemisinin leads to inhibition of viability and proliferation, and apoptosis of SMMC-7721 cells. Furthermore, we observed that holotransferrin significantly enhanced the anti-cancer activity of artemisinin. This study may provide a potential therapeutic choice for liver cancer.

Hypoglycemic Activity and Antioxidative Stress of Extracts and Corymbiferin from Swertia bimaculata In Vitro and In Vivo.

The present study was to investigate the anti-diabetic activities of Swertia bimaculata. Based on the glucose consumption of S. bimaculata extractsand different fractions (petroleum, dichloromethane, ethyl acetate, n-butanol and water extracts) in 3T3-L1 adipocyte assay, ethanol (ETH) and dichloromethane (DTH) extracts had the most effective potency. Furthermore, ETH, DTH and corymbiferin (the most abundant component of DTH) were evaluated for anti-diabetic effects in high fat and sucrose fed combined with low dose streptozocin induced diabetic rats. DTH and corymbiferin displayed remarkable anti-diabetic activities. The fasting blood glucose levels were significantly decreased, while the serum insulin levels were obviously increased. The oral glucose tolerance was also improved. The lowed serum total cholesterol, low density lipoprotein (LDL) and triglyceride levels and increased ratio of HDL (high density lipoprotein)/LDL were observed. The insulin sensitivity was improved on the basis of increased expressions of insulin-receptor substrate-2, phosphatidylinositol 3-kinase and Ser/Thr kinase AKT2. And also DTH and corymbiferin improved antioxidant capacity and carbohydrate metabolism in diabetic rats, along with the improvement of histopathology of livers and pancreatic ß cells. Corymbiferin was one of active constituents, responsible for anti-diabetic properties. Therefore, S. bimaculata could be considered as an alternative agent against diabetes mellitus.

Antidiabetic effects of Swertia macrosperma extracts in diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Swertia macrosperma is a traditional folk medicine used for its anti-hepatitis, antipyretic and antidotal effects as "Dida" or "Zangyinchen" in Tibet, Yunnan and Guizhou province for a long time, and it has been reported for its anti-diabetic effects in a Chinese patent. Swertia macrosperma was reported rich in xanthones, iridoids, seco-iridoids and their glycosides, several of which had been documented as potential antidiabetic agents. The objective of this study was to investigate the antidiabetic effect of Swertia macrosperma in diabetic rats. MATERIALS AND METHODS: This study was designed firstly to evaluate the effect of Swertia macrosperma on glucose consumption in HepG2 cells. Based on the result in HepG2 cells, the antidiabetic effect of ethanol extract (EE) and n-butanol extract (BE) were investigated in diabetic rats induced by high fat fed and streptozotocin. The effects of EE and BE on fasting blood glucose, oral glucose tolerance test, serum insulin, glycosylated hemoglobin, serum lipid level, serum antioxidant parameters, glucokinase, glucose-6-phosphatase activities and glycogen content in liver tissue were measured, histology examination of pancreatic tissue was also carried out. RESULTS: After 4 weeks treatment with EE and BE, apparently decreased fasting blood glucose concentrations were observed in these treated groups, compared with the diabetic control groups. Additionally, improvement in serum antioxidant parameters and lipid profile were evidenced clearly. Moreover, EE and BE had effects of protecting the pancreatic ß-cells and stimulating insulin secretion from the remaining pancreatic ß-cells, evidenced by pancreatic histology examination. Increased glucokinase activity and decreased glucose-6-phosphatase activity were observed in liver. CONCLUSION: The results of in vivo and in vitro experiment suggested that EE and BE of Swertia macrosperma had excellent effects on controlling the hyperglycemia and hyperlipidemia in diabetic rats.

Preventive effects of polysaccharides from Liriope spicata var. prolifera on diabetic nephropathy in rats.

This study was undertaken to investigate preventive effects of polysaccharides (LSP) from Liriope spicata var. prolifera on diabetic nephropathy in rats, which were induced by high fat-fed and low-dose streptozotocin (STZ). The levels of fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) in diabetic rats were significantly decreased after treated with LSP for 28 days. Additional, the glucose tolerance of diabetes rats showed improvement after administration of LSP. The results also indicated that LSP were able to normalize hyperlipidemia, ameliorate oxidative stress, improve renal function parameters, inhibit the structural damages of kidney tissue and down-regulate the system of advanced glycation end products - receptor for advanced glycation end products (AGE-RAGE). In conclusion, LSP had potential preventive effects on diabetic nephropathy in diabetic rats.

Hyperglycemia induces the variations of 11ß-hydroxysteroid dehydrogenase type 1 and peroxisome proliferator-activated receptor-γ expression in hippocampus and hypothalamus of diabetic rats.

In this paper, we first observed that there were differences in expressions of 11ß-HSD1 and PPAR-γ, in hippocampi and hypothalami, among constant hyperglycemia group, control group and the fluctuant glycemia group, using Immunohistochemical analysis. However, whether in expression o f 11ß-HSD1 or PPAR-γ, there were no statistic differences between the control group or the fluctuant glycemia group. So, we removed the fluctuant glycemia group, retaining only constant hyperglycemia group and control group, being fed for 8 weeks. After 8 weeks of induction, 11ß-HSD1 expression increased and PPAR-γ expression decreased in the constant hyperglycemia group compared with control group, both in hippocampi and hypothalami, by Western Blot. The constant hyperglycemia group also showed impaired cognition in MORRIS watermaze, lower serum corticosterone level, and higher Serum ACTH concentration after 8 weeks. We inferred that the cognition impairment may be related to the abnormal expression of 11ß-HSD1 and PPAR-γ in central nerves system. As for 11ß-HSD1 is a regulating enzyme, converting the inactive 11-dehydrocorticosterone into the active glucocorticoid corticosterone, thus amplifying GC action in local tissues. It is also well known that high local GC levels can affect the cognitive function. In addition, PPAR-a protective receptor, which is related to cognition.

[Changes of endogenous ouabain in rat serum and certain tissues after exposure to simulated weightlessness].

OBJECTIVE: To investigate the changes of endogenous ouabain (EO) in rat serum and some tissues after exposure to simulated weightlessness and to investigate its possible pathophysiology. METHOD: Male Wistar rats were randomly divided into control group (Con) and 1 week tail-suspension group (TS). Enzyme-linked immunosorbent assay (ELISA) was used to detect the content of EO in serum, hypothalamus, pituitary, adrenal gland, kidney, heart and liver. RESULT: Compared with Con, EO increased significantly in serum, hypothalamus, adrenal gland and kidney after tail suspension (P<0.05). CONCLUSION: Simulated weightlessness induced changes of EO in serum and some tissues, which may have some effects on the regulation of hydro-electrolyte metabolism and cardiovascular functions.

[Research of ginsenosides in kou zi qi using HPLC-MS-MS].

AIM: To analyze the ginsenosides in Kou zi qi (rhizomes of Panax japonicus C. A. Mey. var. major (Burkill) C. Y. Wu et K. M. Feng), and to supply evidences for chemotaxanology of Panax species and clinical uses of Kou zi qi. METHODS: The ginsenosides were isolated by HPLC, then the positive- and negative-ion API-MS/MS of constituents collected from HPLC were measured. RESULTS: Eight ginsenosides were identified as ginsenoside Re, ginsenoside Ro, chikuseksusaponins IV, IVa, notoginsenoside R2, ginsenosides Rb1, Rc and Rd, respectively, based on comparison of retention time with those of standards by HPLC, and analysis on their API-MS/MS data. Ginsenoside Ro and chikuseksusaponin IVa are the major components of Kou zi qi. CONCLUSION: This plant had a close relationship to P. stipuleanatus, P. zinginensis and P. japonicus var major; a relatively remote relationship to P. ginseng and P. quinquefolius, in a view of chemotaxanology. Ginsenoside Ro and chikuseksusaponin IVa might be the anti-inflammatory constituents of Kou zi qi.

[Clinical observation on treatment of acute myelocytic leukemia by supplementing qi, nourishing yin and clearing heat principle].

OBJECTIVE: To observe the clinical efficacy of TCM with supplementing Qi, nourishing Yin and clearing heat principle (SQNYCH) combined with chemotherapy in treating myelocytic leukemia. METHODS: One hundred and fourteen patients were randomly divided into the treated group (n = 68) and the control group (n = 46). To the treated group, SQNYCH was applied as the basic treatment, with combined chemotherapeutic protocol, using DA, HA and IA, to induce remission, and to the M3 patients, all-trans retinoic acid and arsenic trioxide were given. As for patients in the control group, only western medicine was administered. RESULTS: In the treated group 49 patients (72.1%) were completely remitted, 9 (13.2%) partially remitted and the total remission rate being 85.3%, which was significantly different from that in the control group. After treatment, the blood and bone marrow picture were obviously improved in both groups, but the increase of hemoglobin and platelet were better in the treated group than in the control group (P < 0.05 or P < 0.01). Immune functions were enhanced in both groups, but the elevation of CD4, CD4/CD8 ratio and NK cells were higher in the treated group than in the control group (P < 0.05 and P < 0.01). CONCLUSION: Application of SQNYCH principle in treating acute myelocytic leukemia could elevate the clinical efficacy, which is of great value in clinical practice.