Role and targeting of the AGC kinase family in pulmonary fibrosis (Review).

Pulmonary fibrosis (PF) is a progressive and irreversible pulmonary disease with a high mortality rate and limited treatment options. The cAMP-dependent protein kinase A, cGMP-dependent protein kinase G and phospholipid-dependent protein kinase C, collectively known as AGC kinases, are evolutionarily conserved protein kinases that are widely distributed among eukaryotes. AGC kinases serve a crucial role in a variety of cellular functions and pathological processes, including cancer, diabetes, inflammation and viral infections, where they have been implicated the pathogenesis of PF. The present review summarizes the evidence for the involvement of specific AGC kinases in the pathogenesis of PF, and provides a theoretical basis for the development of targeted AGC kinase small molecule inhibitors or targeted drugs, offering more effective treatment options and strategies for patients with PF.

Differential Diagnosis of Fulminant Myocarditis and Acute Coronary Syndromes in the Case of Failure of Coronary Angiography: A Case Report.

Fulminant myocarditis (FM) is a severe disease with a rapidly progressive and life-threatening course caused mainly by viral infection. The symptoms, laboratory findings, and presence of ECG changes resemble acute coronary syndrome. Therefore, coronary angiography is usually helpful in making the appropriate diagnosis. However, failure to obtain complete coronary artery images due to coronary artery anatomic variations poses a challenge for the diagnosis of FM. Here, we report a case of FM preliminarily diagnosed as acute coronary syndrome (ACS) due to the presence of coronary artery anomaly.

The Mechanisms of Sevoflurane-Induced Neuroinflammation.

Sevoflurane is one of the most commonly used inhaled anesthetics due to its low blood gas coefficient, fast onset, low airway irritation, and aromatic smell. However, recent studies have reported that sevoflurane exposure may have deleterious effects on cognitive function. Although neuroinflammation was most widely mentioned among the established mechanisms of sevoflurane-induced cognitive dysfunction, its upstream mechanisms have yet to be illustrated. Thus, we reviewed the relevant literature and discussed the most mentioned mechanisms, including the modulation of the microglial function, blood-brain barrier (BBB) breakdown, changes in gut microbiota, and ease of cholinergic neurotransmission to help us understand the properties of sevoflurane, providing us new perspectives for the prevention of sevoflurane-induced cognitive impairment.

Dexmedetomidine Mitigated NLRP3-Mediated Neuroinflammation via the Ubiquitin-Autophagy Pathway to Improve Perioperative Neurocognitive Disorder in Mice.

Background: Surgery and anesthesia-induced perioperative neurocognitive disorder (PND) are closely related to NOD-like receptors (NLR) family, pyrin domain containing 3 (NLRP3) inflammasome microglia inflammatory response. Inhibiting the occurrence of neuroinflammation is an important treatment method to improve postoperative delirium. Fewer NLRP3-targeting molecules are currently available in the clinic to reduce the incidence of postoperative delirium. Dexmedetomidine (DEX), an α2 adrenergic receptor agonist has been shown to have antioxidant and anti-inflammatory activities. The present study showed that DEX reduced the production of cleaved caspase1 (CASP1) and destroyed the NLRP3-PYD And CARD Domain Containing (PYCARD)-CASP1 complex assembly, thereby reducing the secretion of IL-1ß interleukin beta (IL-1ß). DEX promoted the autophagy process of microglia and reduced NLRP3 expression. More interestingly, it promoted the ubiquitination and degradation of NLRP3. Thus, this study demonstrated that DEX reduced NLRP3-mediated inflammation through the activation of the ubiquitin-autophagy pathway. This study provided a new mechanism for treating PND using DEX. Methods: C57BL/6 mice were pre-administered DEX 3 days in advance, and an abdominal exploration model was used to establish a perioperative neurocognitive disorder model. The anti-inflammatory effect of DEX was explored in vivo by detecting NLRP3-CASP1/IL-1ß protein expression and behavioral testing. Primary microglia were stimulated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP) in vitro, the expression of CASP1 and IL-1ß was detected in the supernatant of cells, and the expression of autophagy-related proteins microtubule-associated protein 1 light chain 3 beta (MAP1LC3B) and sequestosome 1 (SQSTM1) was examined in the cytoplasm. Meanwhile, Co-immunoprecipitation (Co-IP) was used to detect NLRP3 protein ubiquitination so as to clarify the new mechanism underlying the anti-inflammatory effect of DEX. Results: Pre-administration of DEX reduced the protein expression of NLRP3, CASP1, and IL-1ß in the hippocampus of mice induced by surgery and also improved the impairment of learning and memory ability. At the same time, DEX also effectively relieved the decrease in spine density of the hippocampal brain induced by surgery. DEX decreased the cleaved CASP1 expression, blocked the assembly of NLRP3-PYCARD-CASP1 complex, and also reduced the secretion of mature IL-1ß in vitro. Mechanically, it accelerated the degradation of NLRP3 inflammasome via the autophagy-ubiquitin pathway and reduced the green fluorescent protein/red fluorescent protein MAP1LC3B ratio, which was comparable to the effect when using the autophagy activator rapamycin (Rapa). Furthermore, it increased the ubiquitination of NLRP3 after LPS plus ATP stimulated microglia. Conclusion: DEX attenuated the hippocampal brain inflammation by promoting NLRP3 inflammasome degradation via the autophagy-ubiquitin pathway, thus improving cognitive impairment in mice.

[Effect of new simple breathing apparatus on oxygen therapy in patients with severe and critical coronavirus disease 2019].

OBJECTIVE: To make a new simple respirator and observe the oxygen therapy effect of the respirator on patients with severe and critical coronavirus disease 2019 (COVID-19). METHODS: Based on the infectivity and hospital requirements of COVID-19, a new simple respirator was designed by the medical staff of the Department of Anesthesiology of the Second Affiliated Hospital of Nanchang University, which was applied on the 22 patients with severe and critical COVID-19 who needed oxygen therapy admitted to the Cancer Center of Tongji Medical College of Huazhong University of Science and Technology from February 15th to March 15th in 2020. The new simple respirator contained two National Utility Model Patents (a respirator: ZL 2015 2 0410623.6, a fluid switch and oxygen suction device: ZL 2017 2 0873509.6), which was mainly composed of anesthesia mask and filter, L-shaped connecting tube, soft breathing bladder, connecting tube and elastic fixing belt. When in use, the anesthesia mask was fixed to the patient's mouth and nose with elastic straps, the connecting tube was inserted into the oxygen meter interface, the oxygen flow was adjusted to 6-10 L/min, and the L-shaped connecting tube was opened immediately after the soft breathing bag was full. The carbon dioxide and excess oxygen in the body was discharged from exhaust port. The oxygen flow was lowered to 2-3 L/min, the patient's respiratory rate (RR) was observed through the soft breathing bag fluctuations, and the oxygen flow was adjusted at any time. The changes of pulse oxygen saturation (SpO2), RR and heart rate (HR) before and after application of new simple respirator were observed, and the blood gas test results of part of the patients were collected. RESULTS: Twenty-two patients with severe and critical COVID-19 had significantly higher SpO2 at 10 minutes after application of the new simple ventilator than before application (0.994±0.007 vs. 0.952±0.017, P < 0.01), and RR was significantly lower than that before application (times/min: 27.59±3.63 vs. 29.64±3.81, P < 0.01); after 1 day of application, each index was further improved. All 13 patients who received blood gas analysis indicated no carbon dioxide accumulation. CONCLUSIONS: The new simple respirator can significantly improve the oxygen therapy effect of patients with severe and critical COVID-19. At the same time, 2019 novel coronavirus (2019-nCoV) can be filtered through the filter to reduce the formation of aerosol and protect the medical staff and patients.

[Effects of cumulative parthenogenetic generation and age of amictic female on the reproduction of rotifer Brachionus calyciflorus].

Effects of cumulative parthenogenetic generation and age of amictic female on mictic female production and fecundity of the rotifer Brachionus calyciflorus were studied by means of individual culture. The results showed that percentage of total mictic females produced by the parental females in each of four generations increased with the increasing generations. More mictic females were produced from younger maternal amictic females. Amictic offspring from older mothers produced more mictic daughters. There was no significant effect of the cumulative parthenogenetic generation on the mean number of eggs produced by amictic females per life cycle, and no significant effect of the age of amictic female on the mean number of eggs produced by the offspring of amictic female.

[Relationship between sexual reproduction, population growth and resting egg production of freshwater rotifer Brachionus calyciflorus].

Using exponential and logistic growth models, the effects of sexual reproduction frequency and the proportion of a female's daughters reproducing sexually on population growth rate and resting egg production of freshwater rotifer Brachionus calyciflorus were examined by computer simulation. Within the parameters of the simulation, the percentage of micitc females in the offspring required for maximum resting egg production increased from 9% to 69%, when the frequency of sexual reproduction decreased from 100% to 20%. The increase of density-dependent limitation (the value of K decreased from 1000 to 100) made this percentage increase from 18% to 69%, and resting egg production decrease from 1072.10 to 133.67. The relationship between the population growth rate (r) and the optimum percentage of mictic females in the offspring required for maximum resting egg production was best described by curvilinear regression. When sexual reproduction became more frequent and density-dependent decreased, The population with the percentage of mictic females in the offspring in 10-30% had a bigger resting egg production.