Astaxanthin protective barrier and its ability to improve the health in patients with COVID-19.

Inflammation acts like a double-edged sword and can be harmful if not appropriately controlled. COVID-19 is created through a novel species of coronavirus SARS-CoV-2 (2019-nCoV). Elevated levels of inflammatory factors such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), etc. lead to Acute Respiratory Distress Syndrome (ARDS) and severe complications of infection in the lungs of coronavirus-infected patients. Astaxanthin is a natural and potent carotenoid with powerful antioxidant activity as well as an anti-inflammatory agent that supports good health. The effects of astaxanthin on the regulation of cyclooxygenase-2 (COX-2) pathways and the reduction and suppression of cytokines and other inflammatory agents such as IL-6 and TNF-α have already been identified. Therefore, these unique features can make this natural compound an excellent option to minimize inflammation and its consequences.

ATF4 activation promotes hepatic mitochondrial dysfunction by repressing NRF1-TFAM signalling in alcoholic steatohepatitis.

OBJECTIVE: Mitochondrial dysfunction plays a dominant role in the pathogenesis of alcoholic liver disease (ALD); however, the underlying mechanisms remain to be fully understood. We previously found that hepatic activating transcription factor 4 (ATF4) activation was associated with mitochondrial dysfunction in ALD. This study aimed to investigate the function and mechanism of ATF4 in alcohol-induced hepatic mitochondrial dysfunction. DESIGN: ATF4 activation was detected in the livers of patients with severe alcoholic hepatitis (AH). The role of ATF4 and mitochondrial transcription factor A (TFAM) in alcohol-induced liver damage was determined in hepatocyte-specific ATF4 knockout mice and liver-specific TFAM overexpression mice, respectively. RESULTS: Hepatic PERK-eIF2α-ATF4 ER stress signalling was upregulated in patients with AH. Hepatocyte-specific ablation of ATF4 in mice ameliorated alcohol-induced steatohepatitis. ATF4 ablation also attenuated alcohol-impaired mitochondrial biogenesis and respiratory function along with the restoration of TFAM. Cell studies confirmed that TFAM expression was negatively regulated by ATF4. TFAM silencing in hepatoma cells abrogated the protective effects of ATF4 knockdown on ethanol-mediated mitochondrial dysfunction and cell death. Moreover, hepatocyte-specific TFAM overexpression in mice attenuated alcohol-induced mitochondrial dysfunction and liver damage. Mechanistic studies revealed that ATF4 repressed the transcription activity of nuclear respiratory factor 1 (NRF1), a key regulator of TFAM, through binding to its promoter region. Clinical relevance among ATF4 activation, NRF1-TFAM pathway disruption and mitochondrial dysfunction was validated in the livers of patients with AH. CONCLUSION: This study demonstrates that hepatic ATF4 plays a pathological role in alcohol-induced mitochondrial dysfunction and liver injury by disrupting the NRF1-TFAM pathway.

Major Improvement in Wound Healing Through Pharmacologic Mobilization of Stem Cells in Severely Diabetic Rats.

Current therapeutic strategies for diabetic foot ulcer (DFU) have focused on developing topical healing agents, but few agents have controlled prospective data to support their effectiveness in promoting wound healing. We tested a stem cell mobilizing therapy for DFU using a combination of AMD3100 and low-dose FK506 (tacrolimus) (AF) in streptozocin-induced type 1 diabetic (T1DM) rats and type 2 diabetic Goto-Kakizaki (GK) rats that had developed peripheral artery disease and neuropathy. Here, we show that the time for healing back wounds in T1DM rats was reduced from 27 to 19 days, and the foot wound healing time was reduced from 25 to 20 days by treatment with AF (subcutaneously, every other day). Similarly, in GK rats treated with AF, the healing time on back wounds was reduced from 26 to 21 days. Further, this shortened healing time was accompanied by reduced scar and by regeneration of hair follicles. We found that AF therapy mobilized and recruited bone marrow-derived CD133+ and CD34+ endothelial progenitor cells and Ym1/2+ M2 macrophages into the wound sites, associated with enhanced capillary and hair follicle neogenesis. Moreover, AF therapy improved microcirculation in diabetic and neuropathic feet in GK rats. This study provides a novel systemic therapy for healing DFU.

A case series of pulmonary hypertension in small infants with atrial septal defect.

BACKGROUND: Atrial septal defect (ASD) is one of the most common congenital heart defects (CHDs) with prevalence of 8% to 10% in children with CHD and incidence of 56 per 100000 live births. It is categorized according to the defect site in which the most common form is secundum ASD (ASD2) with the defect in the central part of the atrial septum. CASE REPORT: In our case series, we evaluated five children aged under one year old with ASD2 and pulmonary hypertension (PH). All the patients were referred for surgical ASD closure. Their PH was improved and the size of right atrium (RA) and right ventricle (RV) became normal during the follow-up and one year after the surgery all of them had normal pulmonary artery pressure (PAP) with normal RA and RV size. CONCLUSION: According to our study and those done by others, the prevalence of PH in infants with ASD is low, but when this combination is found without any other CHD, ASD closure should be considered.

Pharmacological Mobilization and Recruitment of Stem Cells in Rats Stops Abdominal Adhesions After Laparotomy.

Adhesions are a very common complication in the abdominal surgery. Animal studies and human trials have evaluated strategies designed to reduce and prevent postsurgical adhesions but few have an evidence base that justifies routine use. A strategy to prevent adhesions effectively remains an urgent need. We studied a reproducible model of intra-peritoneal adhesion formation in rats using laparotomy with several peritoneal sutures to produce the adhesions. Here we show that entraining endogenous stem cells into injury sites using the combined effect of AMD3100 and low-dose FK-506 (AF) can reduce the adhesion score significantly and abolish peritoneal adhesions in 45% of animals in a rat model of severe postsurgical intra-abdominal adhesions, compared with saline controls. Searching for mechanisms, we found AF treatment dramatically increased SDF-1 expressing cells, HGF expressing Ym1+ M2 macrophages and CD133+ stem cells in the injury sites of peritoneal surface at day 5 post-operation. Our results demonstrate that medically induced recruitment of autologous stem cells using AF significantly reduced postsurgical intra-abdominal adhesions. These findings suggest a novel effective therapeutic approach to preventing adhesions in patients.

Phosphodiesterase 4 Inhibition as a Therapeutic Target for Alcoholic Liver Disease: From Bedside to Bench.

Alcoholic liver disease (ALD) is a major cause of liver-related mortality. There is still no US Food and Drug Administration-approved therapy for ALD, and therefore, identifying therapeutic targets is needed. Our previous work demonstrated that ethanol exposure leads to up-regulation of cAMP-degrading phosphodiesterase 4 (PDE4) expression, which compromises normal cAMP signaling in monocytes/macrophages and hepatocytes. This effect of ethanol on cAMP signaling contributes to dysregulated inflammatory response and altered lipid metabolism. It is unknown whether chronic alcohol consumption in humans alters hepatic PDE4 expression and cAMP signaling and whether inadequate cAMP signaling plays a pathogenic role in alcohol-induced liver injury. Our present work shows that expression of the PDE4 subfamily of enzymes is significantly up-regulated and cAMP levels are markedly decreased in hepatic tissues of patients with severe ALD. We also demonstrate the anti-inflammatory efficacy of roflumilast, a clinically available PDE4 inhibitor, on endotoxin-inducible proinflammatory cytokine production ex vivo in whole blood of patients with alcoholic hepatitis. Moreover, we demonstrate that ethanol-mediated changes in hepatic PDE4 and cAMP levels play a causal role in liver injury in in vivo and in vitro models of ALD. This study employs a drug delivery system that specifically delivers the PDE4 inhibitor rolipram to the liver to avoid central nervous system side effects associated with this drug. Our results show that PDE4 inhibition significantly attenuates ethanol-induced hepatic steatosis and injury through multiple mechanisms, including reduced oxidative and endoplasmic reticulum stress both in vivo and in vitro. Conclusion: Increased PDE4 plays a pathogenic role in the development of ALD; hence, directed interventions aimed at inhibiting PDE4 might be an effective treatment for ALD.

Percutaneous retrieval of an intracardiac central venous port fragment using snare with triple loops.

Peripherally inserted venous ports fracture with embolization in patients who received chemotherapy is a serious and rare complication, and few cases have been reported in children. We report a successful endovascular technique using a snare for retrieving broken peripherally inserted venous ports in a child for chemotherapy. Catheter fragments may cause complications such as cardiac perforation, arrhythmias, sepsis, and pulmonary embolism. A 12-year-old female received chemotherapy for acute lymphocytic leukemia through a central venous port implanted into her right subclavian area. The patient completed chemotherapy without complications 6 months ago. Venous port was accidentally fractured during its removal. Chest radiographs of the patient revealed intracardiac catheter fragment extending from the right subclavian to the right atrium (RA) and looping in the RA. The procedure was performed under ketamine and midazolam anesthesia and fluoroscopic guidance using a percutaneous femoral vein approach. A snare with triple loops (10 mm in diameter) was used to successfully retrieve the catheter fragments without any complication. Percutaneous transcatheter retrieval of catheter fragments is occasionally extremely useful and should be considered by interventional cardiologists for retrieving migrated catheters and can be chosen before resorting to surgery, which has potential risks related to thoracotomy, cardiopulmonary bypass, and general anesthesia.

Postoperative cardiac arrest in children with congenital heart abnormalities.

BACKGROUND: The exact survival rates and markers of survival after postoperative cardiac arrest in children with congenital heart abnormalities are unknown. METHODS: In this one-year study, we identified children younger than seven years of age with postoperative cardiac arrest in our pediatric cardiac intensive care unit database. Parameters from perioperative, pre-arrest, and resuscitation periods were analyzed for these patients. Comparisons were made between survivors and non-survivors after cardiopulmonary resuscitation (CPR). Fisher's exact, Student's t, and chi-square tests were used to analyze data. RESULTS: Of 529 evaluated children who underwent corrective heart surgery, 59 (11%) sustained a documented cardiac arrest. Of these, 22 (37%) survived and regained their vital signs. Perioperative parameters (age, weight, and duration of cardiopulmonary bypass pumping), ventricular physiology, oxygen saturation, and bicarbonate concentration did not influence the outcome of CPR. Greater use of inotropic agents was not associated with higher mortality. A significant relationship was seen between having history of cardiac arrest and CPR success (P < 0.001). CONCLUSION: CPR had undesirable outcomes in patients with hemodynamic dysfunction (i.e. low mean arterial blood pressure). Patients with univentricular physiology or history of cardiac arrest are not prone to a higher risk of mortality following arrest.

Study of sugar beet cyst nematode life cycle using plant tissue culture method.

After optimization of sterilizing of cyst and larva second stage of Heterodera schachtii, possibility of using nematode on seedlings of sugar beet (Beta vulgaris L.) in in vitro conditions were studied using sterilized larvae of beet cyst nematode. For this purpose, non sterile cysts were extracted from infected soil and hatched into zinc chloride solution with concentration of 0.5 g L(-1). Then, for preparation of sterile second stage larvae, several sterilizing treatments were used. Mean comparisons were performed between sterilized live larvae number by Duncan's method. Results showed that 70% ethanol for 1 min followed by 2.5% hypochlorite sodium for 5 minutes and 0.1% hypochlorite sodium for 20 min were best treatments for disinfecting cysts and larvae, respectively. In parallel, two nematode susceptible sugar beet varieties were applied to produce seedlings in in vitro culture. PG(oB) medium containing different hormonal compositions was used for producing of hairy roots and inoculation of seedling with sterilized larvae. After nematode inoculation tests, daily observations were done by counting cysts and stained roots and larvae under stereomicroscope. Between 5-12 cysts formed on the roots of each seedling from two varieties 40 days after inoculation. As a result, it seems that this technique can be used for sugar beet germplasm evaluation to screen nematode resistant genotypes in in vitro controlled condition.

Effects of occupational exposure in pesticide plant on workers' serum and erythrocyte cholinesterase activity.

OBJECTIVES: The determination of cholinesterase activity has been commonly applied in the biomonitoring of exposure to organophosphates and carbamates and in the diagnosis of poisoning with anticholinesterase compounds. One of the groups who are at risk of pesticide intoxication are the workers engaged in the production of these chemicals. AIMS: The aim of this study was to assess the effect of pesticides on erythrocyte and serum cholinesterase activity in workers occupationally exposed to these chemicals. METHODS: The subjects were 63 workers at a pesticide plant. Blood samples were collected before they were employed (phase I) and after 3 months of working in the plant (phase II). Cholinesterase level in erythrocytes (EChE) was determined using the modified Ellman method, and serum cholinesterase (SChE) by butyrylthiocholine substrate assay. RESULTS: The mean EChE levels were 48+/-11 IU/g Hb in phase I and 37+/-17 IU/g Hb in phase II (paired t-test, mean=-29; 95% CI=-43-14), p<0.001). The mean SChE level was 9569+/-2496 IU/l in phase I, and 7970+/-2067 IU/l in phase II (paired t-test, mean=1599; 95% CI=1140-2058, p<0.001). There was a significant increase in ALT level (p < 0.001) and a decrease in serum albumin level (p<0.001). CONCLUSION: In view of the significant decrease in EChE and SChE levels among pesticide workers, it seems that routine assessment of cholinesterase level in workers employed in such occupations and people handling pesticides should be made obligatory.