Electroacupuncture Attenuates Ventilator-Induced Lung Injury by Modulating the Nrf2/HO-1 Pathway.

INTRODUCTION: Ventilator-induced lung injury (VILI) is the most common complication associated with mechanical ventilation. Electroacupuncture (EA) has shown potent anti-inflammatory effects. This study aimed to investigate the effects of EA on VILI and explore the underlying mechanisms. METHODS: Male C57BL/6 mice were subjected to high tidal volume ventilation to induce VILI. Prior to mechanical ventilation, mice received treatment with EA, nonacupoint EA, or EA combined with zinc protoporphyrin. RESULTS: EA treatment significantly improved oxygenation, as indicated by increased PaO2 levels in VILI mice. Moreover, EA reduced lung injury score, lung wet/dry weight ratio, and protein concentration in bronchoalveolar lavage fluid. EA also decreased the expression of pro-inflammatory cytokines including interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, IL-18, chemokine keratinocyte chemoattractant, macrophage inflammatory protein 2, and malondialdehyde. Furthermore, EA increased the activities of antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase in VILI mice. At the molecular level, EA upregulated the expression of Nrf2 (nucleus) and heme oxygenase -1, while down-regulating the expression of p-NF-κB p65, NLR Family Pyrin Domain Containing 3, Cleaved Caspase-1, and ASC in VILI mice. Notably, the effects of EA were reversed by zinc protoporphyrin treatment, nonacupoint EA did not affect the aforementioned indicators of VILI. CONCLUSIONS: EA alleviates VILI by inhibiting the NLR Family Pyrin Domain Containing three inflammasome through activation of the Nrf2/HO-1 pathway.

[Effects of electroacupuncture pretreatment on NLRP3 inflammasome in mice with ventilator-induced lung injury].

OBJECTIVE: To observe the effect of electroacupuncture (EA) pretreatment on inflammatory response in ven-tilator-induced lung injury (VILI) mice, so as to explore the underlying mechanism of EA pretreatment on prevention of VILI. METHODS: C57BL/6 mice were randomly divided into sham-operation group, model group, EA group and sham-acupoint group，with 8 mice in each group. The VILI model was established by ventilation with high tidal volume. Mice in the EA group and sham-acupoint group were given EA at "Zusanli" (ST36)and "Feishu"(BL13) or non-acupoints (located at 1-2 cm on both sides of the tail root of the proximal trunk) before mechanical ventilation, 30 min each time, once a day for 5 days. Arterial blood was collec-ted for blood gas analysis, the total protein content in bronchoalveolar lavage fluid (BALF) was detected by BCA method. The contents of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in BALF were detected by ELISA. Lung injury score was determined after HE staining. The protein expression levels of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and Caspase-1 in lung tissue was detected by Western blot. RESULTS: Compared with the sham-operation group, the arterial partial pressure of oxygen and oxygenation index were decreased(P<0.05), the levels of total protein, IL-1ß and IL-18 in BALF, the W/D value and the pathological injury score of lung tissue and the protein expression levels of NLRP3, Caspase-1 and ASC were increased(P<0.05)in the model group. Following the interventions, the above mentioned increased or decreased indicators were reversed(P<0.05) in the EA group rather than in the sham-acupoint group. CONCLUSION: EA pretreatment of ST36 and BL13 can reduce the damage of lung tissue caused by mechanical ventilation, which may be related to its effect in reducing the expression of NLPR3 inflammasome related proteins, reducing the activation of inflammasome, and thereby reducing the inflammatory response.

The Effect of Electroacupuncture Preconditioning on Regional Cerebral Oxygen Saturation Levels in Elderly Patients with Diabetes.

Objective: This study aimed to evaluate the effect of electroacupuncture preconditioning on regional cerebral oxygen saturation (rSO2) levels in elderly patients with diabetes. Methods: Forty patients undergoing elective diabetic foot surgery were enrolled in this study. All patients were aged 65 years and above and weighed 45-75 kg. All were characterized as class II or III according to the American Society of Anesthesiologists' physical status classification system. Patients were divided randomly into an electroacupuncture group (group E) and a control group (group C); both groups comprised 20 patients. In group E, the DU20 (Baihui), DU24 (Shenting), and EX-HN1 (Sishencong) acupoints were selected for electroacupuncture 30 min prior to administering anesthesia, while in group C, patients underwent routine anesthesia without electroacupuncture. The patients in both groups were anesthetized using a sciatic nerve block. The number of cases with increased or decreased regional oxygen saturation (rSO2) compared with the baseline as well as rSO2 variability in the two groups were recorded and compared. Results: There was no significant difference in the preoperative rSO2 values between the two groups (54.4 ± 4.8 (L), 53.9 ± 5.2 (R) [group C] vs 54.1 ± 5.2 (L), 54.5 ± 4.6 (R)[group E]). Compared with group C, the rSO2 in group E increased (50.3 ± 3.9 [group C] vs 58.4 ± 3.2[group E]), and this difference was statistically significant (P < 0.001). Conclusion: Electroacupuncture stimulation can increase rSO2 levels in patients with diabetes. Clinical Registration Number: ChiCTR2100048783 (http://www.chictr.org.cn).

The Preventive Effect of Transcutaneous Electrical Acupoint Stimulation on Postoperative Delirium in Elderly Patients with Time Factors: A Randomized Trial.

Objectives: There is currently no exact and effective treatment for postoperative delirium (POD). The purpose of this study was to observe the effect of transcutaneous electrical acupoint stimulation (TEAS) before surgery and during surgery in elderly patients with POD. Materials and Methods: A total of 90 patients were randomly divided into three groups: a preoperative TEAS group (group E1), an intraoperative TEAS group (group E2), and a control group (group C). In group E1, TEAS was applied at the Shenting, Baihui, bilateral Neiguan, and Hegu points for 30 min 1 day before surgery and before the induction of anesthesia. In group E2, TEAS was applied during surgery. In group C, electrodes were applied to the points just cited, but no electric stimulation was administered. The incidence of delirium was assessed within 5 days after surgery, and the plasma concentration of propofol at bispectral index (BIS) = 50 was recorded. Blood samples were collected to measure neuron-specific enolation (NSE), tumor necrosis factor-α (TNF-α), and interleukin (IL)-1ß 1 day before surgery and 1 and 5 days after surgery. Results: The incidence of delirium in group E1 was decreased in comparison with group C and group E1 (both p < 0.05). The propofol plasma concentration at BIS = 50 in group E1 was also decreased in comparison with group C and group E2 (both p < 0.05). Compared with group C, the concentrations of NSE, TNF-α, and IL-1ß in plasma were decreased in group E1 and group E2 1 and 5 days after surgery (both p < 0.05), and the concentrations of NSE and IL-1ß in plasma in group E1 were decreased 1 and 5 days after surgery in comparison with group E2. Conclusion: The TEAS can reduce the dosage of propofol required during surgery and the occurrence of delirium after surgery. Its mechanism may be related to inhibiting inflammation response and alleviating brain injury. Compared with intraoperative application, the effect of preconditioning with TEAS before surgery is better. Clinical Trial Registration: ChiCTR-INR-17012501. Date of registration: August 29, 2017.

Serum CathepsinD in pregnancy: Relation with metabolic and inflammatory markers and effects of fish oils and probiotics.

BACKGROUND AND AIMS: Elevated circulating levels of CathepsinD (CatD) have been linked to metabolic deviations including liver inflammation. We investigated 1) whether supplementation with probiotics and/or fish oil affects CatD and 2) whether the CatD concentration would associate with gestational diabetes (GDM), low-grade inflammation, lipid metabolism, body fat % and dietary composition. METHODS AND RESULTS: Overweight/obese pregnant women (n = 438) were randomized into fish oil + placebo, probiotics + placebo, fish oil + probiotics or placebo + placebo groups. Fish oil contained 1.9 g docosahexaenoic acid and 0.22 g eicosapentaenoic acid and probiotics were Lacticaseibacillusrhamnosus HN001 (formerly Lactobacillusrhamnosus HN001) and Bifidobacteriumanimalis ssp. lactis 420, 1010 colony-forming units each). Serum CatD levels were analysed by ELISA, GlycA and lipid metabolites by NMR, high sensitive C-reactive protein (hsCRP) by immunoassay, and intakes of energy yielding nutrients and n-3 and n-6 fatty acids from food diaries at both early and late pregnancy. GDM was diagnosed by OGTT. CatD concentrations did not differ between the intervention groups or by GDM status. Multivariable linear models revealed that body fat % and GlycA affected CatD differently in healthy women and those with GDM. CONCLUSION: The serum CatD concentration of pregnant women was not modified by this dietary intervention. Serum CatD was influenced by two parameters, body fat and low grade inflammation, which were dependent on the woman's GDM status. CLINICAL TRIAL REG. NO: NCT01922791, clinicaltrials.gov (secondary analysis).

Glycyrrhetinic acid and its derivatives as potential alternative medicine to relieve symptoms in nonhospitalized COVID-19 patients.

SARS-CoV-2 is highly infectious, and infection by this virus results in COVID-19, manifesting predominantly symptoms in the lower respiratory system. Detection of viral genomic materials by RT-PCR is the gold standard for diagnosis. Suspected COVID-19 patients who had a documented history of exposure and exhibited symptoms, but did not have positive PCR test results, were generally self-quarantined with prescriptions aiming to help attenuate their symptoms. These prescriptions are however neither specific nor highly effective for COVID-19 treatment. Given the rapidly growing pandemic and the overwhelmed medical system, the number of self-quarantined patients is increasing. There is an urgent need of alternative medicine to help patients relieve symptoms during self-quarantine, and to potentially help increase their chances of survival and recovery from the infection. We report here a case of severe COVID-19 that never had a positive PCR test result during disease progression but was confirmed with antibody test post recovery. This patient was self-quarantined and received diammonium glycyrrhizinate (DG), a steroid-like molecule, in combination with vitamin C as alternative medicine. This patient went through severe COVID-19 but eventually recovered upon the implementation of this treatment regimen, suggesting potential therapeutic effects of DG as alternative medicine to help relieve COVID-19 symptoms.

Baicalein Induces Autophagy and Apoptosis through AMPK Pathway in Human Glioma Cells.

Baicalein (BAI) is a natural flavonoid. It has been shown that BAI has anticancer effects, but the molecular mechanism is still unclear. The aim of the current study was to confirm whether or not BAI triggers autophagy and induces AMPK activation in glioma U251 cells. The Ad-mcherry-GFP-LC3B adenovirus experiments indicated that BAI induces glioma cell autophagy. Western blotting showed that the level of LC3II expression increased with the time and concentration of BAI. Following treatment with chloroquine, the expression of LC3 was enhanced Immunofluorescence also confirmed this result. At the same time, cleaved caspase-3, DAPI staining, and JC-1 staining revealed that apoptosis was also induced in the induction of autophagy. In addition, we found that BAI activates phosphorylation of AMPK, which is further confirmed using compound C in this process. When the phosphorylation of AMPK was inhibited, autophagy, and apoptosis were also inhibited. In conclusion, BAI induces autophagy and apoptosis through AMPK pathway. Surprisingly, our research provides new insight with the function of anticancer of BAI, and the potential of the promotion in glioma cell apoptosis might be related to autophagy activation. These results demonstrate the anticancer activity of BAI, which can be used as potential therapeutic agents for cancer therapy.

The Functional Study of a Chinese Herbal Compounded Antidepressant Medicine--Jie Yu Chu Fan Capsule on Chronic Unpredictable Mild Stress Mouse Model.

Jie Yu Chu Fan capsule (JYCF) is a new compounded Chinese herbal medicine for the treatment of depression. The present study was designed to explore the antidepressant effects and the possible mechanisms of JYCF by using chronic unpredictable mild stress (CUMS) mouse model and comparing results to that of fluoxetine. Behavioral tests including an open field test, sucrose preference test and forced swim test were performed to evaluate the antidepressant effects of JYCF. The concentrations of monoamine neurotransmitters and metabolic products including norepinephrine (NE), 5-hydroxytryptamine (5-HT), dopamine (DA), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the cerebral cortex and hippocampus of mice were determined by means of high performance liquid chromatography with electrochemical detection (HPLC-EC). The results show that a successful mouse CUMS model was established through 5 weeks of continuous unpredictable stimulation, as indicated by the significant decrease in sucrose preference and locomotor activity and increase in immobility time in the forced swim test. Chronic treatment of JYCF (1.25, 2.5 and 5 g/kg) and fluoxetine (20 mg/kg) significantly reversed the CUMS-induced behavioral abnormalities. JYCF (1.25, 2.5 and 5 g/kg) significantly increased NE in CUMS mouse prefrontal cortex (P < 0.01, P < 0.01, P < 0.05 respectively) and 5-HT in hippocampus (P < 0.05). In summary, our findings suggest that JYCF exerts comparable antidepressant-like effects to that of fluoxetine in CUMS mice. Besides, the antidepressant-like effect of JYCF is mediated by the increase of monoaminergic transmitters including 5-HT and NE.