HBO1 as an Important Target for the Treatment of CCL4-Induced Liver Fibrosis and Aged-Related Liver Aging and Fibrosis.

The liver is the largest digestive organ in the human body. The increasing incidence of chronic liver fibrosis is one of the major health challenges in the world. Liver fibrosis is a wound-healing response to acute or chronic cellular damage of liver tissue. At present, despite a series of research progress on the pathophysiological mechanism of fibrosis that has been made, there is still a gap in identifying antifibrotic targets and converting them into effective treatments. Therefore, it is extremely important to seek a molecular target that can alleviate or reverse liver fibrosis, which has important scientific and clinical significance. In the current study, to evaluate the therapeutic effect of HBO1 as a molecular target on liver aging and fibrosis, naturally-aged mice and CCL4-induced liver fibrosis mice were used as animal models, and multiple experiments were performed. Experimental results showed that HBO1 knockdown could strongly mitigate the accumulation of hepatic collagen by Masson and Sirius Red staining. Further study showed that HBO1 knockdown reduced the expression of fibrosis-related marker molecules (α-SMA, collagen type I (ColI), and fibronectin). Further work showed that HBO1 knockdown could significantly alleviate HSC activation. On this basis, we analyzed the underlying mechanism by which HBO1 alleviates liver fibrosis. It was found that HBO1 knockdown may modulate liver fibrosis by regulating the processes of EMT, inflammation, and oxidative stress. We further studied the effect of HBO1 knockdown on liver aging and aging-related liver fibrosis, and the results showed that HBO1 knockdown could significantly reduce the level of aging-related liver fibrosis and relieve liver aging. In conclusion, we systematically investigated the potential of HBO1 as a therapeutic target to attenuate liver fibrosis and liver aging. The current study found a crucial target for liver fibrosis and liver-aging therapy, which has laid a solid foundation for the liver fibrosis-related research.

Hyperbaric oxygen therapy in a patient with Guillain-Barré syndrome receiving mechanical ventilation.

The mortality rate of patients with Guillain-Barré syndrome (GBS) who develop respiratory muscle paralysis and need mechanical ventilation is increased. Though an unestablished indication, hyperbaric oxygen treatment (HBOT) has been used to treat patients with mild GBS who do not have respiratory muscle paralysis. The use of HBOT in severe cases has not been reported. We present a patient with severe GBS who received HBOT while ventilated in a multiplace hyperbaric chamber. Three courses of HBOT (one session per day, 10 sessions per course) were administered with a 2-day rest period between each course. The HBOT protocol was 40 minutes at 220 kPa with 25 minutes of compression and decompression. Following weeks of gradual deterioration, motor function improved after the first HBOT session. After eight HBOT sessions, the patient was successfully discontinued from mechanical ventilation and after 10 sessions the patient's muscle strength was significantly improved. After 30 HBOT sessions, the patient had normal breathing and speech, and did not cough when eating. Upper limb muscle strength was graded as 4 on the Medical Research Council (MRC) scale, lower limb muscle strength was graded as MRC 3. The patient was successfully discharged. Mechanically ventilated GBS patients may benefit from HBOT but studies are required to separate spontaneous recovery rates from treatment benefit.

Successful rescue using tracheal intubation cannula for severe central airway stenosis after tracheotomy: A CARE compliant case report.

INTRODUCTION: Central airway stenosis is a life-threating requiring immediate medical intervention. There are several options for treating central airway stenosis, including rigid bronchoscopy, bronchoscopic high-power laser therapy, high-frequency electric needle knife, and balloon-expanding stents. However, interventional techniques may be unavailable in an emergent situation or at smaller local hospitals. In this case report, we publicly demonstrate for the first time that a tracheal intubation catheter may be applied as a temporary alternative to interventional bronchoscopic treatment. PATIENT CONCERNS: A 72-year old male patient was admitted with a 1-year history of intermittent dyspnea, which was exacerbated for one day. One day prior to admission to our hospital, the patient presented with cyanosis due to an exacerbation of dyspnea.A tracheotomy was performed and the patient had been carrying a tracheotomy cannula for 6 months. DIAGNOSIS: The ventilator alarm indicated high airway resistance and the nurses were unable to insert the suction pipes into the airway. Immediate fiberoptic bronchoscopy showed diffuse edema and stenosis of the inferior tracheal airways. INTERVENTIONS: Tracheal intubation was used to temporarily replace the tracheotomy cannula, which successfully expanded the narrowed airways. OUTCOMES: The blood oxygen saturation returned to normal, and dyspnea was quickly relieved. CONCLUSION: In emergent situations, tracheal intubation catheters may be used in patients with post-tracheotomy central airway stenosis, not only for surviving the most dangerous phase but for also prolonging the survival time for further treatments.

Ulinastatin suppresses endoplasmic reticulum stress and apoptosis in the hippocampus of rats with acute paraquat poisoning.

Lung injury is the main manifestation of paraquat poisoning. Few studies have addressed brain damage after paraquat poisoning. Ulinastatin is a protease inhibitor that can effectively stabilize lysosomal membranes, prevent cell damage, and reduce the production of free radicals. This study assumed that ulinastatin would exert these effects on brain tissues that had been poisoned with paraquat. Rat models of paraquat poisoning were intraperitoneally injected with ulinastatin. Simultaneously, rats in the control group were administered normal saline. Hematoxylin-eosin staining showed that most hippocampal cells were contracted and nucleoli had disappeared in the paraquat group. Fewer cells in the hippocampus were concentrated and nucleoli had disappeared in the ulinastatin group. Western blot assay showed that expressions of GRP78 and cleaved-caspase-3 were significantly lower in the ulinastatin group than in the paraquat group. Immunohistochemical findings showed that CHOP immunoreactivity was significantly lower in the ulinastatin group than in the paraquat group. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining showed that the number of apoptotic cells was reduced in the paraquat and ulinastatin groups. These data confirmed that endoplasmic reticular stress can be induced by acute paraquat poisoning. Ulinastatin can effectively inhibit this stress as well as cell apoptosis, thereby exerting a neuroprotective effect.

[The effect of selective phosphatase inhibitors Salubrinal on autophagy and apoptosis in the lung tissue of rats with acute paraquat poisoning].

OBJECTIVE: To investigate the effect of selective phosphatase inhibitors Salubrinal on autophagy and apoptosis in the lung tissue of rats with acute paraquat (PQ) poisoning, and to explore its mechanism. METHODS: 200 Wistar rats were randomly divided into four groups by randomized arrangement table formed by computer, with 50 rats in each group. PQ poisoning model was reproduced by one time gastric lavage with 1 mL of 40 mg/kg PQ solution followed by intraperitoneal injection of 1 mL normal saline (NS) once a day. The rats in control group were lavaged once with 1 mL of NS followed by intraperitoneal injection of 1 mL NS twice a day. The rats in Sal 0.5 and Sal 1.0 groups were intraperitoneal injected with 1 mL Salubrinal 0.5 mg/kg or 1.0 mg/kg on the 1st, 3rd, and 5th day after PQ poisoning once a day. The lung tissue was harvested on the 7th day after poisoning, and the changes in histomorphology were observed using hematoxylin and eosin (HE) staining. The positive expression of autophagy-related protein LC3-II in lung tissue was observed after immunohistochemistry staining, and LC3-II and caspase-3 protein expressions were determined by Western Blot. RESULTS: HE staining results showed partial abnormal pulmonary structure in the PQ poisoning group: collapse of pulmonary alveoli, enlargement of the cavity, local infiltration of inflammatory cells, increasing thickness in the alveoli wall and obvious bleeding in the local lung tissue. Compared with the PQ poisoning group, the above changes in Sal 0.5 and Sal 1.0 groups were obviously relieved. It was shown by immunohistochemistry staining that compared with control group, the positive expression of LC3-II was obviously decreased in the PQ poisoning group, Sal 0.5, and Sal 1.0 groups (A value: 78.34 ± 10.71, 76.52 ± 8.21, 77.48 ± 9.11 vs. 117.58 ± 15.26, all P<0.05). There was no significant difference in positive expression of LC3-II between each of the later three groups (all P>0.05). Western Blot results showed: compared with the control group, the protein expressions of LC3-II and caspase-3 were significantly increased in PQ poisoning group [LC3-II (A value): 0.22 ± 0.05 vs. 0.14 ± 0.03, caspase-3 (A value): 0.115 ± 0.013 vs. 0.023 ± 0.006, both P<0.05]. Compared with PQ poisoning group, the protein expressions of LC3-II and caspase-3 were obviously decreased in the Sal 0.5 and Sal 1.0 groups [LC3-II (A value): 0.19 ± 0.05, 0.18 ± 0.04 vs. 0.22 ± 0.05; caspase-3(A value): 0.078 ± 0.012, 0.076 ± 0.010 vs. 0.115 ± 0.013, all P<0.05]. CONCLUSIONS: The endoplasmic reticulum stress-autophagy is activated in the pulmonary cell of acute PQ poisoning rats. Salubrinal can decrease the autophagy and apoptosis in the lung of rats with acute PQ poisoning, which play a role in the treatment.