Transplant of fecal microbiota from healthy young mice relieves cognitive defects in late-stage diabetic mice by reducing metabolic disorders and neuroinflammation.

Fecal microbiota transplant (FMT) is becoming as a promising area of interest for treating refractory diseases. In this study, we investigated the effects of FMT on diabetes-associated cognitive defects in mice as well as the underlying mechanisms. Fecal microbiota was prepared from 8-week-aged healthy mice. Late-stage type 1 diabetics (T1D) mice with a 30-week history of streptozotocin-induced diabetics were treated with antibiotics for 7 days, and then were transplanted with bacterial suspension (100 µL, i.g.) once a day for 14 days. We found that FMT from healthy young mice significantly alleviated cognitive defects of late-stage T1D mice assessed in Morris water maze test. We revealed that FMT significantly reduced the relative abundance of Gram-negative bacteria in the gut microbiota and enhanced intestinal barrier integrity, mitigating LPS translocation into the bloodstream and NLRP3 inflammasome activation in the hippocampus, thereby reducing T1D-induced neuronal loss and astrocytic proliferation. FMT also reshaped the metabolic phenotypes in the hippocampus of T1D mice especially for alanine, aspartate and glutamate metabolism. Moreover, we showed that application of aspartate (0.1 mM) significantly inhibited NLRP3 inflammasome activation and IL-1ß production in BV2 cells under a HG/LPS condition. We conclude that FMT can effectively relieve T1D-associated cognitive decline via reducing the gut-brain metabolic disorders and neuroinflammation, providing a potential therapeutic approach for diabetes-related brain disorders in clinic.

Therapeutic Window of Intravenous Immunoglobulin (IVIG) and its correlation with IVIG-resistant in Kawasaki Disease: a retrospective study

Abstract Objective: To investigate the optimal timing of initial intravenous immunoglobulin (IVIG) treatment in Kawasaki disease (KD) patients. Methods: KD patients were classified as the early group (day 1-4), conventional group (day 5-7), conventional group (day 8-10), and late group (after day 10). Differences among the groups were analyzed by ANOVA and Chi-square analysis. Predictors of IVIG resistance and the optimal cut-off value were determined by multiple logistic regression analyses and receiver operating characteristic (ROC) curve analysis. Results: There were no significant differences in IVIG resistance among the 4 groups (p = 0.335). The sensitivity analysis also confirmed no difference in the IVIG resistance between those who started the initial IVIG ≤ day 7 of illness and those who received IVIG >day 7 of illness (p = 0.761). In addition, patients who received IVIG administration more than 7 days from the onset had a higher proportion of coronary artery abnormalities (p = 0.034) and longer length of hospitalization (p = 0.033) than those who started IVIG administration less than 7 days. The optimal cut-off value of initial IVIG administration time for predicting IVIG resistance was >7 days, with a sensitivity of 75.25% and specificity of 82.41%. Conclusions: IVIG therapy within 7 days of illness is found to be more effective for reducing the risk of coronary artery abnormalities than those who received IVIG >day 7 of illness. IVIG treatment within the 7 days of illness seems to be the optimal therapeutic window of IVIG. However, further prospective studies with long-term follow-up are required.

Protective effects of combined treatment with ciprofol and mild therapeutic hypothermia during cerebral ischemia-reperfusion injury.

Despite improvement in cardiopulmonary resuscitation (CPR) performance, cardiac arrest (CA) is still associated with poor prognosis. The high mortality rate is due to multi-organ dysfunction caused by cerebral ischemia and reperfusion injury (I/R). The guidelines for CPR suggest the use of therapeutic hypothermia (TH) as an effective treatment to decrease mortality and the only approach confirmed to reduce I/R injury. During TH, sedative agents (propofol) and analgesia agents (fentanyl) are commonly used to prevent shiver and pain. However, propofol has been associated with a number of serious adverse effects such as metabolic acidosis, cardiac asystole, myocardial failure, and death. In addition, mild TH alters the pharmacokinetics of agents (propofol and fentanyl) and reduces their systemic clearance. For CA patients undergoing TH, propofol can be overdosed, leading to delayed awakening, prolonged mechanical ventilation, and other subsequent complications. Ciprofol (HSK3486) is a novel anesthetic agent that is convenient and easy to administer intravenously outside the operating room. Ciprofol is rapidly metabolized and accumulates at low concentrations after continuous infusion in a stable circulatory system compared to propofol. Therefore, we hypothesized that treatment with HSK3486 and mild TH after CA could protect the brain and other organs.

Further undescribed cembranoids from South China Sea soft coral Sarcophyton ehrenbergi: Structural elucidation and biological evaluation.

A detailed chemical investigation of the South China Sea soft coral Sarcophyton ehrenbergi has yield seven undescribed cembranoids, namely isoehrenbergol D and sarcoehrenolides F-K embodying a rare α,ß-unsaturated-lactone moiety at C-6 to C-19, along with two known related compounds, ehrenbergol D and sarcoehrenolide A. Their structures and absolute configurations were unambiguously established in the light of extensive spectroscopic data analysis, modified Mosher's method, X-ray diffraction analysis, and quantum chemical computation method. In a bioassay for α-glucosidase inhibition, ehrenbergol D was evaluated as α-glucosidase inhibitor with an IC50 value of 13.57 µM.

Therapeutic Window of Intravenous Immunoglobulin (IVIG) and its correlation with IVIG-resistant in Kawasaki Disease: a retrospective study.

OBJECTIVE: To investigate the optimal timing of initial intravenous immunoglobulin (IVIG) treatment in Kawasaki disease (KD) patients. METHODS: KD patients were classified as the early group (day 1-4), conventional group (day 5-7), conventional group (day 8-10), and late group (after day 10). Differences among the groups were analyzed by ANOVA and Chi-square analysis. Predictors of IVIG resistance and the optimal cut-off value were determined by multiple logistic regression analyses and receiver operating characteristic (ROC) curve analysis. RESULTS: There were no significant differences in IVIG resistance among the 4 groups (p = 0.335). The sensitivity analysis also confirmed no difference in the IVIG resistance between those who started the initial IVIG ≤ day 7 of illness and those who received IVIG >day 7 of illness (p = 0.761). In addition, patients who received IVIG administration more than 7 days from the onset had a higher proportion of coronary artery abnormalities (p = 0.034) and longer length of hospitalization (p = 0.033) than those who started IVIG administration less than 7 days. The optimal cut-off value of initial IVIG administration time for predicting IVIG resistance was >7 days, with a sensitivity of 75.25% and specificity of 82.41%. CONCLUSIONS: IVIG therapy within 7 days of illness is found to be more effective for reducing the risk of coronary artery abnormalities than those who received IVIG >day 7 of illness. IVIG treatment within the 7 days of illness seems to be the optimal therapeutic window of IVIG. However, further prospective studies with long-term follow-up are required.

Lactation mastitis: Promising alternative indicators for early diagnosis.

Although lactation mastitis (LM) has been extensively researched, the incidence rate of LM remains a salient clinical problem. To reduce this incidence rate and achieve a better prognosis, early and specific quantitative indicators are particularly important. It has been found that milk electrolyte concentrations (chloride, potassium, and sodium) and electrical conductivity (EC) significantly change in the early stages of LM in an animal model. Several studies have evaluated EC for the detection of subclinical mastitis in cows. EC, chloride, and sodium content of milk were more accurate for predicting infection status than were other variables. In the early stages of LM, lactic sodium, chloride, and EC increase, but potassium decreases. However, these indicators have not been reported in the diagnosis of LM in humans. This review summarizes the pathogenesis and the mechanism of LM in terms of milk electrolyte concentration and EC, and aim to provide new ideas for the detection of sub-clinical mastitis in humans.

Uncommon Capnosane Diterpenes with Neuroprotective Potential from South China Sea Soft Coral Sarcophyton boettgeri.

The first investigation of the South China Sea soft coral Sarcophyton boettgeri afforded five new capnosane diterpenes, sarboettgerins A-E (1-5), together with one known related compound, pavidolide D (6). Their structures, including absolute configurations, were elucidated by the extensive spectroscopic analysis, 13C NMR calculations, and X-ray diffraction. Among them, new compounds 1-5 were featured by the rarely encountered Z-geometry double bond Δ1 within the 5/11-fused bicyclic capnosane carbon framework. Plausible biogenetic relationships of all isolates were proposed, and they might give an insight into future biomimetic synthesis of these novel compounds. In an in vitro bioassay, compound 5 displayed potent anti-neuroinflammatory activity against LPS-induced NO release in BV-2 microglial cells, which might be developed as a new type of potential neuroprotective agent in future.

NF-κB: A novel therapeutic pathway for gastroesophageal reflux disease?

Although gastroesophageal reflux disease (GERD), a common chronic disease in clinical practice, has been widely studied, its potential adverse impact on patients is still a significant clinical concern. It is necessary to understand the pathogenesis of the disease and choose appropriate treatment according to its mechanism. The pathogenesis of GERD is diverse and complex. As the traditional treatment methods are expensive and ineffective in alleviating symptoms in some patients, new treatment options need to be explored. Our previous study suggested that the activation of nuclear factor-kappa beta (NF-κB) in esophageal mucosa may be related to the injury of epithelial barrier function caused by reflux. Based on the literature and our previous study results, it is speculated that inhibition of NF-κB activation may block the insult of GERD on the esophageal mucosal barrier. NF-κB may play an important role in the development of GERD. This article reviews the pathogenesis of GERD and the relationship between NF-κB and GERD, in order to provide new strategies for the treatment of GERD.

Unusual Secondary Metabolites from the Mangrove Ecosystems: Structures, Bioactivities, Chemical, and Bio-Syntheses.

Mangrove ecosystems are widely distributed in the intertidal zone of tropical and subtropical estuaries or coasts, containing abundant biological communities, for example, mangrove plants and diverse groups of microorganisms, featuring various bioactive secondary metabolites. We surveyed the literature from 2010 to 2022, resulting in a collection of 134 secondary metabolites, and classified them into two major families in terms of the biological sources and 15 subfamilies according to the chemical structures. To highlight the structural diversity and bioactivities of the mangrove ecosystem-associated secondary metabolites, we presented the chemical structures, bioactivities, biosynthesis, and chemical syntheses.

The Use of Bioelectrical Impedance Analysis Measures for Predicting Clinical Outcomes in Critically Ill Children.

Background: The study aimed to investigate the association of bioelectrical impedance analysis (BIA) for predicting clinical outcomes in critically ill children. Methods: This single-center prospective observational study included patients admitted to a mixed Pediatric Intensive Care Unit (PICU). All patients underwent anthropometric measurement and BIA measurements in the first 24 h of admission. The patients were classified into different groups based on body mass index (BMI) for age. Electronic hospital medical records were reviewed to collect clinical data for each patient. All the obtained data were analyzed by the statistical methods. Results: There were 231 patients enrolled in our study, of which 31.6% were diagnosed with malnutrition. The phase angle (PhA) of 90-day survivors was significantly higher than that of the non-survivors (4.3° ± 1.1°vs. 3.1° ± 0.9°, P = 0.02). The age-adjusted Spearman partial correlation analysis showed a weak negative correlation between PhA and duration of medical ventilation (rs = -0.42, P < 0.05). Furthermore, length of stay in PICU has a very weak correlation with ECW/TBW (rs = 0.29, P < 0.05), and a negative correlation with protein (rs = -0.27, P < 0.05). Multivariate analysis found that PhA was a significant predictor associated with the 90-day mortality when it was adjusted for PRISM III score (adjusted OR = 1.51, CI: 1.10-2.07, p = 0.01). The area under the ROC (AUROC) of PhA for predicting 90-day mortality was 0.69 (95% CI: 0.53-0.85, p < 0.05), and the cutoff value of PhA was 3.0°, with a sensitivity and specificity of 83 and 53%, respectively. Conclusion: BIA-derived PhA was found to be an independent predictor of 90-day mortality among critically ill children. A low PhA was associated with a prolonged duration of medical ventilation.

Design and semisynthesis of oleanolic acid derivatives as VEGF inhibitors: Inhibition of VEGF-induced proliferation, angiogenesis, and VEGFR2 activation in HUVECs.

Angiogenesis inhibitors targeting the VEGF signaling pathway are developed into drugs for the treatment of vaious diseases, such as cancer, rheumatoid arthritis, and age-related macular degeneration. Recent studies have revealed that oleanolic acid (OA), a natural pentacyclic triterpenoid, inhibited the VEGF/VEGFR2 signaling pathway and angiogenesis in HUVECs, which may represent an attractive VEGF inhibitor. In this paper, rational structural modification towards OA was performed in order to improve its inhibitory effects aganist VEGF and anti-angiogenesis potential. As a result, a series of novel OA derivatives, possessing α,ß-unsaturated ketone system in ring A and amide functional group at C-28, were prepared and evaluated for cytotoxicity and their ability to inhibit VEGF-induced abnormal proliferation of HUVECs. The results showed that two promising derivatives, OA-1 and OA-16, exhibited no in vitro cytotoxicity against HUVECs but showed more potent inhibitory activity against VEGF-induced proliferation and angiogenesis in HUVECs, compared with OA. The results of Western blot indicated that OA-1 and OA-16 inhibited VEGF-induced VEGFR2 activation. Furthermore, small interfering RNA experiments were performed to confirm that both compounds inhibited VEGF-induced angiogenesis via VEGFR2. Thus, the present study resulted in the discovery of new promising OA-inspired VEGF inhibitors, which can serve as potential lead compounds for the treatment of angiogenesis-related diseases.

Lung injury after cardiopulmonary bypass: Alternative treatment prospects.

Although the lung injury caused by cardiopulmonary bypass (CPB) has been extensively investigated, the incidence and mortality of lung injury after CPB remain a prominent clinical problem. The poor outcome has been attributed to multifactorial etiology, including the systemic inflammatory response and ischemia reperfusion (I/R) injury during CPB. Lung injury after CPB is a complex pathophysiological process and has many clinical manifestations of mild to severe disease. Which is associated with prognosis. To alleviate this lung injury, interventions that address the pathogenesis are particularly important. This review summarizes the pathogenesis, mechanism and treatment options of lung injury after CPB, such as lung protection with intralipid.

Chemical constituents from the South China sea soft coral Sinularia humilis.

A new diterpenoid with an unusual capnosane skeleton, sinuhumilol A (1), alone with twelve known diverse compounds (2-13), were isolated from the South China Sea soft coral Sinularia humilis. Their structures and stereochemistry were elucidated by extensive spectroscopic analysis, quantum chemical calculations, and/or by the comparison of the spectroscopic data with those reported in the literature. In bioassay, compound 11 exhibited interesting specific cytotoxicity against the human colon adenocarcinoma cell line HT-29 with IC50 value of 12.5 µM.