Clinical characteristics of survivors versus non-survivors after acute diquat poisoning: a comparative study.

The aim of this study was to compare the clinical characteristics between survivors and non-survivors after acute diquat (DQ) poisoning. Patients treated in the Emergency Department of Fu Yang People's Hospital for DQ poisoning between January 2018 and February 2022 were enrolled in this retrospective comparative study. A total of 65 patients were collected, including 36 males (55.4%) and 29 females (44.6%). There were 34 survivors (52.3%), and 31 non-survivors (47.7%). Patients in the non-survivor group were significantly older (P = 0.003), received a higher dose of DQ before admission (P < 0.001), had more severe organ damage (P < 0.001), lower respiration rate (P < 0.001) and enema (P = 0.009), lower GCS score (P = 0.038), and higher SIRS score (P = 0.018) and APACHE-II score (P < 0.001) than patients in the survivor group. Additionally, biochemical indicators after admission between survivors and non-survivors were significantly different (all P < 0.05). Multivariate logistic regression analysis showed that respiratory failure (P = 0.021), the dose of DQ (P = 0.022), respiratory rate (P = 0.007), and highest alanine transaminase (ALT) level after admission (P = 0.030) were independent risk factors for acute DQ-induced death. These data suggest that non-survivors with acute DQ poisoning are more likely to suffer from respiratory failure, have higher respiratory rate and ALT after admission, and are exposed higher doses of DQ before admission than survivors.

Salidroside suppresses proliferation and migration in prostate cancer via the PI3K/AKT pathway.

BACKGROUND: Prostate cancer (PCa) is one of the most common malignancies in men. PCa is difficult to detect in its early stages, and most patients are diagnosed in the middle to late stages. At present, drug therapy for advanced PCa is still insufficient. Some patients develop drug resistance in the later stage of therapy, which leads to tumor recurrence, metastasis and even treatment failure. Therefore, it is crucial to find new and effective drugs to treat prostate cancer. OBJECTIVE: The aim of this study was to investigate the anti-cancer effect of salidroside, an active ingredient in a traditional Chinese herbal medicine, on PCa. METHODS: Two human PCa cell lines, PC3 and DU145, were cultured and treated with salidroside. Cell viability and proliferation ability were analyzed through CCK-8 and colony assays, and cell migration ability was detected by Transwell and Scratch assays. RT-PCR and WB were used to detected the expression levels of moleculars related to cell proliferation, apoptosis, migration, and AKT signaling pathway. Forthmore, we performed rescue experiments with agonist to verify the affected signaling pathway. RESULTS: Salidroside inhibited the proliferation, colony formation, and migration of PCa cells. Meanwhile, apoptosis of PCa cells was enhanced. Moreover, salidroside inhibited PI3K/AKT pathway in PCa cells. The treatment of AKT agonist 740Y-P abrogated the inhibitory effect of salidroside on the PI3K/AKT signaling pathway. CONCLUSIONS: Our study demonstrated that in PCa cells, salidroside inhibites proliferation and migration and promots apoptosis via inhibiting PI3K/AKT pathway.

Worenine Prevents Solar Ultraviolet-Induced Sunburn by Inhibiting JNK2.

Excessive solar ultraviolet (SUV) radiation often causes dermatitis, photoaging, and even skin cancer. In the pathological processes of SUV-induced sunburn, JNK is activated by phosphorylation, and it in turn phosphorylates its downstream transcription factors, such as ATF2 and c-jun. The transcription factors further regulate the expression of pro-inflammatory genes, such as IL-6 and TNF-α, which ultimately leads to dermatitis. Therefore, inhibiting JNK may be a strategy to prevent dermatitis. In this study, we screened for worenine as a potential drug candidate for inhibiting sunburn. We determined that worenine inhibited the JNK-ATF2/c-jun signaling pathway and the secretion of IL-6 and TNF-α in cell culture and in vivo, confirming the role of worenine in inhibiting sunburn. Furthermore, we determined that worenine bound and inhibited JNK2 activity in vitro through the MST, kinase, and in vitro kinase assays. Therefore, worenine might be a promising drug candidate for the prevention and treatment of SUV-induced sunburn.

Vitamin D Supplementation in Exclusively Breastfed Infants Is Associated with Alterations in the Fecal Microbiome.

Breastfeeding and introduction of solid food are the two major components of infant feeding practices that influence gut microbiota composition in early infancy. However, it is unclear whether additional factors influence the microbiota of infants either exclusively breastfed or not breastfed. We obtained 194 fecal samples from infants at 3-9 months of age, extracted DNA, and sequenced the V4 region of the 16S rRNA gene. Feeding practices and clinical information were collected by questionnaire and abstraction of birth certificates. The gut microbiota of infants who were exclusively breastfed displayed significantly lower Shannon diversity (p-adjust < 0.001) and different gut microbiota composition compared to infants who were not breastfed (p-value = 0.001). Among the exclusively breastfed infants, recipients of vitamin D supplements displayed significantly lower Shannon diversity (p-adjust = 0.007), and different gut microbiota composition structure than non-supplemented, breastfed infants (p-value = 0.02). MaAslin analysis identified microbial taxa that associated with breastfeeding and vitamin D supplementation. Breastfeeding and infant vitamin D supplement intake play an important role in shaping infant gut microbiota.

Efficacy of nano-modified Runji ointment in the treatment of mild and moderate psoriasis with blood dryness syndrome: a study protocol for a double-blind randomized controlled trial.

INTRODUCTION: Psoriasis is a common, recurrent, immune skin disease, which seriously affects patients' quality of life. In clinical practice, modified Runji ointment can effectively treat mild-to-moderate psoriasis with blood dryness syndrome, but there is a lack of high-quality evidence-based medical evidence. This trial aims to evaluate the efficacy and safety of nano-modified Runji ointment in the treatment of mild-to-moderate psoriasis with blood dryness syndrome. METHODS/DESIGN: This study will be a randomized double-blind placebo-controlled trial. A total of 80 patients will be recruited and randomly divided into an intervention group (nano-modified Runji ointment group) and a placebo group at a ratio of 1:1. All included patients will receive 8 weeks of nano-modified Runji ointment or placebo ointment respectively, twice a day. The primary outcome will be the change in psoriasis area and disease severity index score at week 8 compared to baseline. The secondary outcomes will be rash area score, pruritus score, Dermatology Life Quality Index score, traditional Chinese medicine symptom score and adverse events. DISCUSSION: This study may provide high-quality evidence for the efficacy of nano-modified Runji ointment in the treatment of mild to moderate psoriasis with blood dryness syndrome. The results of this study will be published in peer-reviewed journals. TRIAL REGISTRATION: ChiCTR, ChiCTR2000034292. Registered July 1, 2020, https://www.chictr.org.cn/edit.aspx?pid=55884&htm=4.

Sarsasapogenin attenuates Alzheimer-like encephalopathy in diabetes.

BACKGROUND: A crosstalk exists between diabetes and Alzheimer's disease (AD), and diabetic encephalopathy displays AD-like disorders. Sarsasapogenin (Sar) has strong anti-inflammatory efficacy, showing neuroprotection and memory-enhancement effects. PURPOSE: This study aims to verify the ameliorative effects of Sar on diabetic encephalopathy in vivo and in vitro, and to clarify the mechanisms from attenuation of AD-like pathology. METHODS: Streptozotocin-induced type 1 diabetic rats and high glucose-cultured SH-SY5Y cells were used in this study. After Sar treatment (20 and 60 mg/kg) for consecutive 9 weeks, Morris water maze and novel object recognition tasks were performed. Hematoxylin-eosin staining was used for examining loss of neurons in CA1 area and ki67 expression for reflecting neurogenesis in DG area of hippocampus. Aß production pathway and tau phosphorylation kinase cascade were examined in these two models. RESULTS: Sar improved learning and memory ability, loss of neurons and reduction of neurogenesis in the hippocampus of diabetic rats. Moreover, Sar suppressed Aß overproduction due to up-regulation of BACE1 in protein and mRNA and tau hyperphosphorylation from inactivation of AKT/GSK-3ß cascade in the hippocampus and cerebral cortex of diabetic rats and high glucose-cultured SH-SY5Y cells, and PPARγ antagonism abolished the effects of Sar on key molecules in the two pathways. Additionally, it was found that high glucose-stimulated Aß overproduction was prior to tau hyperphosphorylation in neurons. CONCLUSION: Sar alleviated diabetic encephalopathy, which was obtained through inhibitions of Aß overproduction and tau hyperphosphorylation mediated by the activation of PPARγ signaling. Hence, Sar is a good candidate compound for AD-like disorders.

Sarsasapogenin ameliorates diabetes-associated memory impairment and neuroinflammation through down-regulation of PAR-1 receptor.

Sarsasapogenin (Sar), a natural steroidal compound, shows neuroprotection, cognition-enhancement, antiinflammation, antithrombosis effects, and so on. However, whether Sar has ameliorative effects on diabetes-associated cognitive impairment remains unknown. In this study, we found that Sar ameliorated diabetes-associated memory impairment in streptozotocin-induced diabetic rats, evidenced by increased numbers of crossing platform and percentage of time spent in the target quadrant in Morris water maze tests, and suppressed the nucleotide-binding domain and leucine-rich repeat containing protein 1 (NLRP1) inflammasome in hippocampus and cerebral cortex. Furthermore, Sar inhibited advanced glycation end-products and its receptor (AGEs/RAGE) axis and suppressed up-regulation of thrombin receptor protease-activated receptor 1 (PAR-1) in cerebral cortex. On the other hand, Sar mitigated high glucose-induced neuronal damages, NLRP1 inflammasome activation, and PAR-1 up-regulation in high glucose-cultured SH-SY5Y cells, but did not affect thrombin activity. Moreover, the effects of Sar were similar to those of a selective PAR-1 antagonist vorapaxar. Further studies indicated that activation of the NLRP1 inflammasome and NF-κB mediated the effect of PAR-1 up-regulation in high glucose condition by using PAR-1 knockdown assay. In summary, this study demonstrated that Sar prevented memory impairment caused by diabetes, which was achieved through suppressing neuroinflammation from activated NLRP1 inflammasome and NF-κB regulated by cerebral PAR-1. HIGHLIGHTS: Sarsasapogenin ameliorated memory impairment caused by diabetes in rats. Sarsasapogenin mitigated neuronal damages and neuroinflammation by down-regulating cerebral PAR-1. The NLRP1 inflammasome and NF-κB signaling mediated the pro-inflammatory effects of PAR-1. Sarsasapogenin was a pleiotropic neuroprotective agent and memory enhancer in diabetic rodents.

Prevalence of inadequate and excessive iodine intake in a US pregnancy cohort.

BACKGROUND: US iodine intake, estimated from the median urinary iodine concentration of population representative data, has declined by half since the 1970s, which is problematic because maternal iodine intake is critical for fetal neurodevelopment. Relying on median urinary concentrations to assess iodine intake of populations is standard practice but does not describe the number of individuals with insufficient intake. Prevalence estimates of inadequate and excessive intake are better for informing public health applications but require multiple urine samples per person; such estimates have been generated in pediatric populations but not yet among pregnant women. OBJECTIVE: Our aims were as follows: (1) to assess median urinary iodine concentrations across pregnancy for comparison with national data and (2) to estimate the prevalence of inadequate and excessive iodine intake among pregnant women in mid-Michigan. STUDY DESIGN: Data were collected from 2008 to 2015 as part of a prospective pregnancy cohort in which women were enrolled at their first prenatal clinic visit. Few exclusion criteria (<18 years or non-English speaking) resulted in a sample of women generally representative of the local community, unselected for any specific health conditions. Urine specimens were obtained as close as practicable to at least 1 specimen per trimester during routine prenatal care throughout pregnancy (n=1-6 specimens per woman) and stored at -80°C until urinary iodine was measured to estimate the iodine intake (n=1014 specimens from 464 women). We assessed urinary iodine across pregnancy by each gestational week of pregnancy and by trimester. We used multiple urine specimens per woman, accounted for within-person variability, performed data transformation to approximate normality, and estimated the prevalence of inadequate and excessive iodine intake using a method commonly employed for assessment of nutrient status. RESULTS: Maternal characteristics reflected the local population in racial and ethnic diversity and socioeconomic status as follows: 53% non-Hispanic white, 22% non-Hispanic black, and 16% Hispanic; 48% had less than or equal to high school education and 71% had an annual income of <$25,000. Median urinary iodine concentrations in the first, second, and third trimester-including some women contributing more than 1 specimen per trimester-were 171 µg/L (n=305 specimens), 181 µg/L (n=366 specimens), and 179 µg/L (n=343 specimens), respectively, with no significant difference by trimester (P=.50, Kruskal-Wallis test for equality of medians). The estimated prevalence of inadequate and excessive iodine intake was 23% and <1%, respectively. CONCLUSION: Median urinary iodine concentrations in each trimester were above the World Health Organization cutoff of 150 µg/L, indicating iodine sufficiency at the group level across pregnancy. However, the estimated prevalence of inadequate iodine intake was substantial at 23%, whereas prevalence of excessive intake was <1%, indicating a need for at least some women to increase consumption of iodine during pregnancy. The American Thyroid Association, the Endocrine Society, and the American Academy of Pediatrics recommend that all pregnant and lactating women receive a daily multivitamin or mineral supplement that contains 150 µg of iodine. The data presented here should encourage the collection of similar data from additional US population samples for the purpose of informing the American College of Obstetricians and Gynecologists' own potential recommendations for prenatal iodine supplementation.

Sarsasapogenin alleviates diabetic nephropathy through suppression of chronic inflammation by down-regulating PAR-1: In vivo and in vitro study.

BACKGROUND: Sarsasapogenin (Sar) shows good effects on diabetic nephropathy (DN) through inhibition of the NLRP3 inflammasome, yet the potential mechanism is not well known. PURPOSE: This study was designed to explore the regulation of thrombin and/or its receptor protease-activated receptor 1 (PAR-1) on the NLRP3 inflammasome and NF-κB signaling in DN condition, and further expounded the molecular mechanism of Sar on DN. METHODS: Streptozotocin-induced diabetic rats were treated by gavage with Sar (0, 20 and 60 mg/kg) for consecutive 10 weeks. Then urine and serum were collected for protein excretion, creatinine, urea nitrogen, and uric acid assay reflecting renal functions, renal tissue sections for periodic acid-Schiff staining and ki67 expression reflecting cell proliferation, and renal cortex for the NLRP3 inflammasome and NF-κB signaling as well as thrombin/PAR-1 signaling. High glucose-cultured human mesangial cells (HMCs) were used to further investigate the effects and mechanisms of Sar. RESULTS: Sar markedly ameliorated the renal functions and mesangial cell proliferation in diabetic rats, and suppressed activation of the NLRP3 inflammasome and NF-κB in renal cortex. Moreover, Sar remarkably down-regulated PAR-1 in protein and mRNA levels but didn't affect thrombin activity in kidney, although thrombin activity was significantly decreased in the renal cortex of diabetic rats. Meanwhile, high glucose induced activation of the NLRP3 inflammasome and NF-κB, and increased PAR-1 expression while didn't change thrombin activity in HMCs; however, Sar co-treatment ameliorated all the above indices. Further studies demonstrated that PAR-1 knockdown attenuated activation of the NLRP3 inflammasome and NF-κB, and Sar addition strengthened these effects in high glucose-cultured HMCs. CONCLUSION: Sar relieved DN in rat through inhibition of the NLRP3 inflammasome and NF-κB by down-regulating PAR-1 in kidney.

Ginkgo biloba extract protects diabetic rats against cerebral ischemia­reperfusion injury by suppressing oxidative stress and upregulating the expression of glutamate transporter 1.

The current study aimed to evaluate the neuroprotective effect of Ginkgo biloba extract (GbE) on the progression of acute cerebral ischemia­reperfusion injury in diabetic rats, and to determine the molecular mechanism associated with this effect. Streptozotocin (STZ) induced diabetic rats were pretreated with GbE (50, 100 and 200 mg/kg/day; intragastric) for 3 weeks. During this period, body weight changes and fasting blood glucose levels were assessed each week. Following pretreatment, rats were subjected to suture occlusion of the middle cerebral artery for 30 min, which was followed by 24 h of reperfusion. Neurological deficits were subsequently evaluated at 2 and 24 h following reperfusion. Rats were sacrificed after 24 h reperfusion, and infarct volume and S100B content were measured to evaluate the neuroprotective effect of GbE. The results of the present study demonstrated that GbE pretreatment improved neurological scores, and reduced cerebral infarct volume and S100B content. Oxidative stress markers, including glutathione (GSH) and superoxide dismutase (SOD) were increased, and malondialdehyde (MDA) contents were reduced following GbE treatment. The levels of p­Akt, p­mTOR and glutamate transporter 1 (GLT1) were observed to be increased in GbE­pretreated rats. These results indicated that GbE pretreatment may serve a protective role against cerebral ischemia­reperfusion injury in diabetic rats by inhibiting oxidative stress reaction, upregulating the expression of Akt/mTOR and promoting GLT1 expression. In conclusion, the current study revealed the protective role and molecular mechanisms of GbE in diabetic rats with cerebral ischemia­reperfusion injury, and may provide novel insight into the future clinical treatment of this condition.

[The Research Advancement and Conception of the Deep-underground Medicine].

The 21th century is the century of exploring and utilizing the underground space. In the future, more and more people will spend more and more time living or/and working in the underground space. However,we know little about the effect on the health of human caused by the underground environment. Herein,we systematically put forward the strategic conception of the deep-underground medicine,in order to reveal relative effects and mechanism of the potential factors in the deep underground space on human's physiological and psychological healthy,and to work out the corresponding countermeasures. The original deep-underground medicine includes the following items. ①To model different depth of underground environment according to various parameters (such as temperature,radiation,air pressure, rock,microorganism), and to explore their quantitative character and effects on human health and mechanism. ② To study the psychological change, maintenance of homeostasis and biothythm of organism in the deep underground space. ③ To learn the association between psychological healthy of human and the depth, structure, physical environment and working time of underground space. ④ To investigate the effect of different terrane and lithology on healthy of human and to deliberate their contribution on organism growth. ⑤ To research the character and their mechanism of growth,metabolism,exchange of energy,response of growth, aging and adaptation of cells living in deep underground space. ⑥ To explore the physiological feature,growth of microbiome and it's interaction with host in the deep underground space. ⑦ To develop deep-underground simulation space, the biologically medical technology and equipments. As a research basis,a deep-underground medical lab under a rock thickness of about 1 470 m has been built,which aims to operate the research of the effect on living organism caused by different depth of underground environment.

Identification and analysis of the stigma and embryo sac-preferential/specific genes in rice pistils.

BACKGROUND: In rice, the pistil is the female reproductive organ, and it consists of two stigmas and an ovary. The stigma is capable of receiving pollen grains and guiding pollen tube growth. The ovary holds the embryo sac, which is fertilized with male gametes to produce seed. However, little is known about the gene function and regulatory networks during these processes in rice. RESULTS: Here, using the RNA-Seq technique, we identified 3531 stigma-preferential genes and 703 stigma-specific genes within the rice pistils, and we verified 13 stigma-specific genes via qRT-PCR and in situ hybridization. The GO analysis showed that the transport-, localization-, membrane-, communication-, and pollination-related genes were significantly enriched in the stigma. Additionally, to identify the embryo sac-preferential/specific genes within the pistils, we compared a wild-type ovary with a mutant dst (defective stigma) ovary and found that 385 genes were down-regulated in dst. Among these genes, 122 exhibited an ovary-specific expression pattern and are thought to be embryo sac-preferential/specific genes within the pistils. Most of them were preferentially expressed, while 14 of them were specifically expressed in the pistil. Moreover, the rice homologs of some Arabidopsis embryo sac-specific genes, which played essential roles during sexual reproduction, were down-regulated in dst. Additionally, we identified 102 novel protein-coding genes, and 6 of them exhibited differences between the stigma and ovary in rice as determined using RT-PCR. CONCLUSIONS: According to these rice ovary comparisons, numerous genes were preferentially or specifically expressed in the stigma, suggesting that they were involved in stigma development or pollination. The GO analysis indicated that a dry rice stigma might primarily perform its function through the cell membrane, which was different from the wet stigma of other species. Moreover, many embryo sac-preferential/specific genes within the pistils were identified and may be expressed in female rice gametophytes, implying that these genes might participate in the process of female gametophyte specialization and fertilization. Therefore, we provide the gene information for investigating the gene function and regulatory networks during female gametophyte development and fertilization. In addition, these novel genes are valuable for the supplementation and perfection of the existing transcriptome in rice, which provides an effective method of detecting novel rice genes.

Cytokines and glucocorticoid receptors are associated with the antidepressant-like effect of alarin.

Little is known about the physiological or pharmacological properties of alarin, a new neuropeptide belonging to the galanin family. We previously showed that alarin has an antidepressant-like effect and is associated with a decrease in the hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis that is observed in patients with depression using unpredictable chronic mild stress (UCMS) mouse model of depression. However, the mechanisms underlying these effects have not been uncovered. Inflammatory cytokines are reportedly associated with depression. Animal studies and cytokine immune therapy in humans suggest that pro-inflammatory cytokines induce depressive symptomatology and potently activate the HPA axis, whereas anti-inflammatory cytokines may decrease activation. Thus, we first determined the levels of inflammatory cytokines in the blood and brain to evaluate whether the antidepressant-like effect of alarin in UCMS-treated mice is related to its regulation of these inflammatory cytokines. Pro-inflammatory cytokines disrupt the function and/or expression of glucocorticoid receptors (GRs), which mediate the negative feedback of glucocorticoids on the HPA axis to keep it from being overactivated. We next explored the expression level of GRs in the brains of mice subjected to UCMS and to the administration of alarin. We found that intracerebroventricular administration of alarin significantly ameliorated depression-like behaviors in the UCMS-treated mice. Alarin restored the UCMS-induced an increase in the levels of the pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor α and a decrease in the anti-inflammatory cytokine IL-10 level in the blood, prefrontal cortex, hippocampus and hypothalamus. Alarin also reversed the UCMS-induced down-regulation of GR expression in these brain regions. Thus, the antidepressant-like effects of alarin may be mediated by restoring altered pro-inflammatory and anti-inflammatory cytokine levels and GR expression to decrease HPA axis hyperactivity. Our findings provide additional knowledge to interpret the pathophysiology of depression.

Tea consumption and leukemia risk: a meta-analysis.

Epidemiologic findings concerning the association between tea consumption and leukemia risk yielded mixed results. We aimed to investigate the association by performing a meta-analysis of all available studies. One cohort studies and six case-control studies with 1,019 cases were identified using PubMed, Web of Science, and EMBASE. We computed summary relative risks (RRs) and 95 % confidence intervals (CIs) using random effect model applied to the relative risk associated with ever, moderate, or highest drinkers vs. non/lowest drinkers. Subgroup analyses were performed based on country (China and USA). Compared with non/lowest drinkers, the combined RR for ever drinkers was 0.76 (95 % CI=0.65-0.89). In subgroup analyses, significant inverse associations were found for both China and USA studies. The summary RR was 0.57 (95 % CI=0.41-0.78) for highest drinkers. Same results were only found in China studies. No significant associations were found for moderate drinkers in overall analysis or in subgroup analyses. There was some evidence of publication bias. In conclusion, this meta-analysis suggests a significant inverse association of high tea consumption and leukemia risk. Results should be interpreted cautiously given the potential publication bias.