Mechanism of Mitophagy and Its Role in Sepsis Induced Organ Dysfunction: A Review.

Autophagy, an evolutionarily conserved process, plays an important role in maintaining cellular homeostasis under physiological and pathophysiological conditions. It is widely believed that mitochondria influence the development of disease by regulating cellular metabolism. When challenged by different stimuli, mitochondria may experience morphological disorders and functional abnormalities, leading to a selective form of autophagy-mitophagy, which can clear damaged mitochondria to promote mitochondrial quality control. Sepsis is a complex global problem with multiple organ dysfunction, often accompanied by manifold mitochondrial damage. Recent studies have shown that autophagy can regulate both innate and acquired immune processes to protect against organ dysfunction in sepsis. Sepsis-induced mitochondrial dysfunction may play a pathophysiological role in the initiation and progression of sepsis-induced organ failure. Mitophagy is reported to be beneficial for sepsis by eliminating disabled mitochondria and maintaining homeostasis to protect against organ failure. In this review, we summarize the recent findings and mechanisms of mitophagy and its involvement in septic organ dysfunction as a potential therapeutic target.

Dexmedetomidine reduces the incidence of postoperative delirium after cardiac surgery: a meta-analysis of randomized controlled trials.

BACKGROUND: The role of dexmedetomidine in preventing postoperative delirium (POD) after cardiac surgery remains controversial because of several recent trials with negative results. We aimed to perform an updated meta-analysis of randomized controlled trials (RCTs) to clarify this controversy. METHODS: RCTs investigating the perioperative administration of dexmedetomidine in cardiac surgery were retrieved from PubMed, Web of Science, and the Cochrane library until August,27,2020. Two researchers independently screened the literature, collected the data and evaluated the bias risk of the included studies. The meta-analysis was performed with the RevMan 5.3. RESULTS: A total of 15 studies including 2813 patients were included in the study. A pooled result showed that dexmedetomidine could reduce the risk of POD in adult population underwent cardiac surgery (OR 0.56, 95%CI 0.36-0.89, P = 0.0004, I2 = 64%). The subgroup analysis demonstrated that the protective effect of dexmedetomidine was only present in the patients injected with dexmedetomidine after surgery but not from the start of surgery, in the adult patients without specific age limitation but not in the elderly, and in the studies in comparison with other sedatives but not with placebo. There were no statistical differences when analyzing the secondary outcomes including hypotension (OR 1.13; 95% CI 0.54-2.37, P < 0.00001, I2 = 85%), bradycardia (OR 1.72; 95% CI 0.84-3.53, P = 0.04, I2 = 58%) and atrial fibrillation (OR 0.87; 95% CI 0.70-1.08, P = 0.43, I2 = 0). CONCLUSIONS: Dexmedetomidine can reduce the incidence of POD compared to other sedatives and opioids after cardiac surgery in adult patients. The proper population and timing for perioperative use of dexmedetomidine after cardiac surgery remain to be further investigated.

Identification and quantification of oleanane triterpenoid saponins and potential analgesic and anti-inflammatory activities from the roots and rhizomes of Panax stipuleanatus.

BACKGROUND: Panax stipuleanatus represents a folk medicine for treatment of inflammation. However, lack of experimental data does not confirm its function. This article aims to investigate the analgesic and anti-inflammatory activities of triterpenoid saponins isolated from P. stipuleanatus. METHODS: The chemical characterization of P. stipuleanatus allowed the identification and quantitation of two major compounds. Analgesic effects of triterpenoid saponins were evaluated in two models of thermal- and chemical-stimulated acute pain. Anti-inflammatory effects of triterpenoid saponins were also evaluated using four models of acetic acid-induced vascular permeability, xylene-induced ear edema, carrageenan-induced paw edema, and cotton pellet-induced granuloma in mice. RESULTS: Two triterpenoid saponins of stipuleanosides R1 (SP-R1) and R2 (SP-R2) were isolated and identified from P. stipuleanatus. The results showed that SP-R1 and SP-R2 significantly increased the latency time to thermal pain in the hot plate test and reduced the writhing response in the acetic acid-induced writhing test. SP-R1 and SP-R2 caused a significant decrease in vascular permeability, ear edema, paw edema, and granuloma formation in inflammatory models. Further studies showed that the levels of inflammatory mediators, nitric oxide, malondialdehyde, tumor necrosis factor-α, and interleukin 6 in paw tissues were downregulated by SP-R1 and SP-R2. In addition, the rational harvest of three- to five-year-old P. stipuleanatus was preferable to obtain a higher level of triterpenoid saponins. SP-R2 showed the highest content in P. stipuleanatus, which had potential as a chemical marker for quality control of P. stipuleanatus. CONCLUSION: This study provides important basic information about utilization of P. stipuleanatus resources for production of active triterpenoid saponins.

Insights into the role of tumor abnormal protein in early diagnosis of cancer: A prospective cohort study.

The aim of this study was to evaluate the clinical use of tumor abnormal protein (TAP) in the diagnosis of different cancers.Totally 394 patients were divided into 4 groups, namely 100 healthy volunteers, 167 patients with cancer, 20 subjects with precancerous lesions, and 107 subjects with benign lesions. TAP was detected in 4 groups of research subjects using a TAP testing kit and examination system. We correlated TAP levels with a wide variety of clinical indicators as well as established cancer markers, including alpha fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19-9). Besides, the changes of TAP level in 51 patients with liver cancer before and after surgery, and overall survival of patients with high or low TAP expression in pancreatic, gallbladder, bile duct, and liver cancers were analyzed.Statistically significant difference was observed in the TAP-positive ratio among subjects with cancer (79.6%) and precancerous lesions (45.0%) compared to the healthy volunteers (4.0%). TAP expression in different cancers was characterized by high sensitivity (79.64%), specificity (89.87%), positive and negative predictive value (85.25% and 85.71%), overall compliance rate (85.53%) but low omission and mistake diagnostic rate (20.36% and 10.13%), Youden index (0.6951). In addition, there was no significant difference among patients with different types of cancer (χ = 2.886, P = .410), and TAP expression was shown to be correlated with AFP in liver cancer (P = .034) but not with CA19-9 in pancreatic cancer (P = .241). Moreover, the overall survival of patients with low expression of TAP in pancreatic, gallbladder, bile duct, and liver cancers were significantly higher than of patients with high expression of TAP. Compared with the preoperative patients with cancer, TAP levels decreased dramatically among postoperative subjects (P < .001).In summary, TAP might hold promise in serving as universal indicator for the diagnosis of different cancers.

Correlation between obstructive sleep apnea and central retinal vein occlusion.

To investigate the possible correlation between obstructive sleep apnea (OSA) and central retinal vein occlusion (CRVO). Thirty consecutive patients with a recent (<3mo) CRVO and an age- and sex-matched group of 30 control subjects were recruited. All subjects underwent full-night polysomnography to measure apnea-hypopnea index (AHI) and oxygen desaturation index (ODI). The average AHI and ODI were significantly higher in CRVO patients (AHI: 13.86±8.63, ODI: 9.21±4.47) than in control subjects (AHI: 8.51±6.36, ODI: 5.87±3.18; P=0.008 and 0.001 respectively). Additionally, the AHI was positively correlated with body mass index (BMI; r=0.476, P=0.017) and ODI (r=0.921, P<0.01) in both CRVO and control subjects. According to AHI scores, twenty-two (73.33%) CRVO patients had OSA and 12 (40.00%) control subjects had OSA, a difference that was statistically significant (P=0.019). OSA may be a risk factor for or a trigger of CRVO development.

Assessment of Exposure to Polybrominated Dipheny Ethers via Inhalation and Diet in China.

OBJECTIVE: This paper is to assess the current status of polybrominated diphenyl ethers (PBDEs) contamination in the environment in China and estimate the exposure to PBDEs in non-occupational populations. METHODS: A total of 80 research papers published from January 2001 to October 2013 were selected. Geographic information system (GIS) was used in mapping PBDE concentrations and distributions in environmental media. Ni's model was applied to calculate ∑PBDE-intake via the intakes of contaminated food, water and air in the Pearl River Delta and Yangtze River Delta. RESULTS: BDE-209 was found to be the major PBDE congener in the environmental media and food in China. PBDE concentrations varied among different areas, among which the contamination in Guangdong Province was most serious. Daily intake of ∑PBDEs was 225.1-446.0 ng/d for adults in the Pearl River Delta, which was higher than the intake for those living in the Yangtze River Delta (148.9-369.8 ng/d). CONCLUSION: Atorvastatin can attenuate LPS-induced TNF-α expression and production by activating HO-1 via the ERK and p38 MAPK pathways, suggesting that atorvastatin can be used in treatment of inflammatory diseases such as sepsis, especially in those with atherosclerotic diseases.

Development of a reference dose for BDE-47, 99, and 209 using benchmark dose methods.

Eleven recently completed toxicological studies were critically reviewed to identify toxicologically significant endpoints and dose-response information. Dose-response data were compiled and entered into the USEPA's benchmark dose software (BMDS) for calculation of a benchmark dose (BMD) and a benchmark dose low (BMDL). After assessing 91 endpoints across the nine studies, a total of 23 of these endpoints were identified for BMD modeling, and BMDL estimates corresponding to various dose-response models were compiled for these separate endpoints. Thyroid, neurobehavior and reproductive endpoints for BDE-47, -99, -209 were quantitatively evaluated. According to methods and feature of each study, different uncertainty factor (UF) value was decided and subsequently reference doses (RfDs) were proposed. Consistent with USEPA, the lowest BMDLs of 2.10, 81.77, and 1698 µg/kg were used to develop RfDs for BDE-47, -99, and -209, respectively. RfDs for BDE-99 and BDE-209 were comparable to EPA results, and however, RfD of BDE-47 was much lower than that of EPA, which may result from that reproductive/developmental proves to be more sensitive than neurobehavior for BDE-47 and the principal study uses very-low-dose exposure.

Gender-specific relationship between prenatal exposure to phthalates and intrauterine growth restriction.

BACKGROUND: No study has examined the association between prenatal phthalate exposure and intrauterine growth retardation (IUGR). This study aimed to investigate whether prenatal exposure to phthalates was associated with increased risk of IUGR. METHODS: A total of 126 mother-newborn pairs, including 42 IUGR cases and 84 control newborns and their mothers, were enrolled in this case-control study. Spot urine samples were collected during the third trimester of pregnancy, and 5 phthalate metabolites (mono-n-butyl phthalate (MBP), monomethyl phthalate (MMP), mono-2-ethylhexyl phthalate (MEHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP)) were measured. RESULTS: Concentrations of MMP, MEHHP, MEOHP, and SumDEHP (MEHP, MEHHP, and MEOHP) were significantly higher in IUGR cases than in normal controls. In all subjects, urinary concentrations of MEHHP and MEOHP were significantly inversely associated with fetal growth indicators (birth weight and Quetelet's index). When mothers were stratified by infant sex, MEHHP and MEOHP concentrations were still negatively associated with fetal growth indicators, while no significant association was observed in females. In addition, exposure-response relationships were observed between MEHHP/SumDEHP concentrations in maternal urine and IUGR. CONCLUSION: Prenatal exposure to phthalates was associated with increased risk of IUGR, and male newborns were more sensitive to phthalates than females.

[The impact of trabeculectomy on ocular surface].

Glaucoma is an eye disease that can lead to irreversible visual impairment. Trabeculectomy remains the most common operation for glaucoma therapy. The formation of functional filtering bleb is the key to the success of surgery. But many studies have found that anti-glaucoma surgeries affected the normal function of the tear film, which can cause the change of the structure of ocular surface resulting in an uncomfortable feeling and dry eye. Most investigators have suggested that the alteration of ocular surface by trabeculectomy is due partially to the damage of ocular surface tissues and topical application of the drugs of anti-metabolism as well as the lack of vascular supply of ultra-thin post-operative filtering bleb.

Exposure levels of environmental endocrine disruptors in mother-newborn pairs in China and their placental transfer characteristics.

There is a growing concern about the potential health effects of exposure to various environmental chemicals during pregnancy and infancy. The placenta is expected to be an effective barrier protecting the developing embryo against some endocrine disruptors (EDs) circulating in maternal blood. The current study was designed to assess in utero exposure levels of non-persistent organic pollutants (non-POPs) and persistent organic pollutants (POPs) in Chinese newborns and potential role of placenta barrier against fetal exposure to these commonly-used environmental endocrine disruptors. A total of 230 newborn-mother pairs were enrolled during 2010-2011, 201 pairs of which were recruited from Shanghai, and the other 29 pairs came from Wenzhou. Maternal blood, cord blood, and meconium specimens were collected in the subject population from Shanghai and analyzed for non-POPs, including mono-2-ethylhexyl phthalate (MEHP), octylphenol (OP) and 4-nonylphenol (4-NP). A total of 19 polybrominated diphenyl ethers (PBDEs) congeners, which belong to POPs, were detected in maternal and cord blood specimens from the other 29 pairs. Fetal-maternal ratios (F-M ratios) and regression coefficients were presented to assess potential function of placenta on barricading the mother/fetal transfer of these EDs. Concentrations of the detected non-POPs in cord blood samples were approximately 20% lower than those in maternal blood, and regression coefficients of which were all over 0.80. In contrast, PBDEs levels in cord blood samples were significantly higher than those in maternal blood. MEHP levels in meconium were much higher than those in cord blood samples, and highly correlated. Therefore, observations demonstrated that the placental barrier slightly decreased the fetal exposure to most non-POPs, while PBDEs seemed to be totally transferred across the placenta and finally reached the fetus. For in utero exposure assessment of Di-2-ethylhexyl phthalate (DEHP), MEHP level in meconium may be a useful biomarker.