Calcineurin controls proximodistal blastema polarity in zebrafish fin regeneration.

Planarian flatworms regenerate their heads and tails from anterior or posterior wounds and this regenerative blastema polarity is controlled by Wnt/ß-catenin signaling. It is well known that a regeneration blastema of appendages of vertebrates such as fish and amphibians grows distally. However, it remains unclear whether a regeneration blastema in vertebrate appendages can grow proximally. Here, we show that a regeneration blastema in zebrafish fins can grow proximally along the proximodistal axis by calcineurin inhibition. We used fin excavation in adult zebrafish to observe unidirectional regeneration from the anterior cut edge (ACE) to the posterior cut edge (PCE) of the cavity and this unidirectional regeneration polarity occurs as the PCE fails to build blastemas. Furthermore, we found that calcineurin activities in the ACE were greater than in the PCE. Calcineurin inhibition induced PCE blastemas, and calcineurin hyperactivation suppressed fin regeneration. Collectively, these findings identify calcineurin as a molecular switch to specify the PCE blastema of the proximodistal axis and regeneration polarity in zebrafish fin.

FGF21 alleviates acute liver injury by inducing the SIRT1-autophagy signalling pathway.

Liver injury can lead to different hepatic diseases, which are the mainly causes of high global mortality and morbidity. Autophagy and Sirtuin type 1 (SIRT1) have been shown protective effects in response to liver injury. Previous studies have showed that Fibroblast growth factor 21 (FGF21) could alleviate acute liver injury (ALI), but the mechanism remains unclear. Here, we verified the relationship among FGF21, autophagy and SIRT1 in carbon tetrachloride (CCl4 )-induced ALI. We established CCl4 -induced ALI models in C57BL/6 mice and the L02 cell line. The results showed that FGF21 was robustly induced in response to stress during the development of ALI. After exogenous FGF21 treatment in ALI models, liver damage in ALI mice was significantly reduced, as well as serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Consistently, FGF21 also greatly reduced the levels of ALT, AST, pro-inflammatory cytokines interleukin 6 (IL6) and tumour necrosis factor-alpha (TNFα) in ALI cell lines. Mechanistically, exogenous FGF21 treatment efficiently upregulated the expression of autophagy marker microtubule-associated protein light chain-3 beta (LC3 II) and autophagy key molecule coiled-coil myosin-like BCL2-interacting protein (Beclin1), which was accompanied by alleviating hepatotoxicity in CCl4 -treated wild-type mice. Then, we examined how FGF21 induced autophagy expression and found that SIRT1 was also upregulated by FGF21 treatment. To further verify our results, we constructed an anti-SIRT1 lentit-RNAi to inhibit SIRT1 expression in mice and L02 cells, which reversed the protective effect of FGF21 on ALI. In summary, these results indicate that FGF21 alleviates ALI by enhancing SIRT1-mediated autophagy.

Effect of Carbon Fiber Nanotubes Tracheotomy Under Swallowing Training Combined with Bronchoscopic Alveolar Lavage.

This study aimed to analyze the effect of carbon fiber nanotube tracheotomy (CFNT) under swallowing training (ST) combined with bronchofiberoscope alveolar lavage (BAL), so as to provide theoretical guidance for the clinical treatment of pulmonary infection. 40 patients with pulmonary infection were selected as the research objects, and the effects of ST combined with BAL were analyzed after CFNT. The patients were randomly divided into four groups: a control group (group A) and three observation groups (groups B, C, and D), with 10 cases in each group. Patients in group A received conventional treatment, patients in group B received conventional treatment + ST, patients in group C received conventional treatment + BAL, and patients in group D received conventional treatment + ST + BAL. The effect of ST + BAL was analyzed after CFNT. The results showed that compared with the group A, the number of lung infections and infection rates in groups C and D was reduced (P < 0.05); the use time and per capita cost of antibiotics in group A were much higher than those in the groups C and D (P < 0.05); and in group B and D, the number of successful extubation of tracheal catheters and the success rate were greatly increased (P < 0.05) and the average time of intubation was dramatically shortened (P < 0.05). The scores of the water swallow test (WST) in groups B and D were much lower than the score of group A (P < 0.05), and the scores for swallowing ability and swallowing dysfunction scores were much different from those of the group A (P < 0.05). In summary, after a CFNT, the lung infection and swallowing function of patients were effectively improved after ST + BAL.

A Novel Balloon Catheter-based Dilation Intervention for Patients with Cricopharyngeus Achalasia After Stroke: A Randomized Study.

This study aimed to investigate the efficacy and safety of a novel balloon catheter in dilation intervention for patients with cricopharyngeus achalasia after stroke. Thirty-four patients with cricopharyngeus achalasia after stroke received routine swallowing rehabilitation training and were randomly assigned to an experimental group (Exp, n = 17) that received dilation therapy using the novel balloon catheter once daily for 5 days per week or a control group (Con, n = 17) that received dilation therapy with a 14-Fr ordinary urinary catheter once daily for 5 days per week. The intervention duration, Eating Assessment Tool (EAT)-10 scores, and Functional Oral Intake Scale (FOIS) scores were recorded at baseline and each day during intervention. The time for a patient's FOIS score to be ≥ 3 as well as the recovery time for oral intake of water, liquid food, mushy food, and solid food were recorded or estimated. Complications were also recorded during intervention. The intervention duration was shorter in the Exp group than in the Con group (p = 0.005). The Exp group patients improved faster than the Con group patients, with a shorter recovery time for oral intake of liquid food (p = 0.002), mushy food (p = 0.001), and solid food (p = 0.001). At the time of intervention termination, EAT-10 scores were lower in the Exp group than in the Con group (p = 0.005). The Exp group had a similar incidence of complications as the Con group but with better tolerability (p = 0.028). Compared with the urinary catheter, the novel balloon catheter for dilation in patients with cricopharyngeus achalasia after stroke may lead to a better and more rapid recovery.

ABCDEF pulmonary rehabilitation program can improve the mid-term lung function of lung cancer patients after thoracoscopic surgery: A randomized controlled study.

Background Pulmonary rehabilitation is recommended for most patients with lung diseases. However, some previous studies have shown that pulmonary rehabilitation has no obvious effect on short-term lung function in patients with lung cancer. Objective The purpose of this study was to evaluate the effect of the ABCDEF pulmonary rehabilitation program on lung cancer patients who have undergone surgery. Design This was a randomized controlled trial with repeated measures. Settings The study was conducted in the Cardiothoracic Surgery Department of a 4000-bed comprising training and research hospital from 2019 to 2020. Participants A total of 90 patients who underwent thoracoscopic pneumonectomy were divided into two groups of 45, using a completely randomized model. Methods Patients in the experimental group participated in an ABCDEF program (Acapella positive vibration pressure training, breathing exercise, cycling training, dance in the square, education, and follow-up) after surgery. In contrast, the regular care provided to the control group focused on breathing and expectoration guidance. The study outcomes were the first second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, 6 min walking distance, Borg score, incidence of postoperative complications, length of indwelling chest tube, and length of postoperative stay. Generalized estimating equation models were used to compare the changes in the outcomes between the groups over time. Results The ABCDEF pulmonary rehabilitation program for patients who underwent thoracoscopic pneumonectomy was found to be more effective in increasing lung function at 3 months after discharge (p<0.05). However, there was no statistically significant difference on the day of discharge (p>0.05). Exercise tolerance was different at both time points (p<0.05). The incidence of postoperative complications in the experimental group was lower than that in the control group (p<0.05). The length of postoperative stay in the experimental group was also shorter (p<0.05), however, the length of the indwelling chest tube was not significantly different between the intervention and control groups (p>0.05). Conclusions This study showed that the ABCDEF pulmonary rehabilitation program could effectively improve mid-term lung function and exercise tolerance in patients after thoracoscopic pneumonectomy, and reduce the incidence of postoperative complications along with the length of postoperative hospital stay.

Nitazoxanide induced myocardial injury in zebrafish embryos by activating oxidative stress response.

Nitazoxanide (NTZ) is a broad-spectrum antiparasitic and antiviral drug (thiazole). However, although NTZ has been extensively used, there are no reports concerning its toxicology in vertebrates. This study used the zebrafish as a vertebrate model to evaluate the safety of NTZ and to analyse the related molecular mechanisms. The experimental results showed that zebrafish embryos exposed to NTZ had cardiac malformation and dysfunction. NTZ also significantly inhibited proliferation and promoted apoptosis in cardiomyocytes. Transcriptomic analysis used compared gene expression levels between zebrafish embryos in the NTZ treatment and the control groups identified 200 upregulated genes and 232 downregulated genes. Analysis by Kyoto encyclopaedia of genes and genomes (KEGG) and gene ontology (GO) showed that signal pathways on cardiomyocyte development were inhibited while the oxidative stress pathways were activated. Further experiments showed that NTZ increased the content of reactive oxygen species (ROS) in the hearts of zebrafish. Antioxidant gadofullerene nanoparticles (GFNPs) significantly alleviated the developmental toxicity to the heart, indicating that NTZ activated the oxidative stress response to cause embryonic cardiomyocyte injury in zebrafish. This study provides evidence that NTZ causes developmental abnormalities in the cardiovascular system of zebrafish.

Punch vs open surgical techniques for placement of bone-anchored hearing implants: a systematic review and meta-analysis of skin reactions and operating time.

PURPOSE: Several authors have reported their experience with the punch technique as compared to open surgical methods for bone-anchored hearing implants (BAHI). However, no study has attempted to aggregate current evidence. We aimed to compare post-operative skin complications and operating time between punch and open surgical techniques of BAHI via a systematic review and meta-analysis. METHODS: Databases of PubMed, Embase, Scopus, BioMed Central, Ovoid, and CENTRAL were screened up to 15th February 2020 to include studies comparing punch and open surgical technique for BAHI. RESULTS: Eight studies were included. Punch technique was compared with dermatome and linear incision techniques with and without soft tissue reduction. There was no difference in normal-to-moderate skin reaction between the punch and open surgical techniques (OR: 0.86 95% CI 0.23, 3.28 I2 = 0%). The incidence of adverse skin reactions were also not different between the two groups. Meta-regression for different follow-up periods did not demonstrate any statistically significant results. Our results also indicated that punch technique requires less operating time, however, the inter-study heterogeneity in the analysis was very high. Similar results were seen on sub-group analysis based on the type of open surgical technique. CONCLUSION: There may be no difference in skin tolerance between the punch technique and open surgical techniques. Operating time may be significantly reduced with the punch technique. Strong conclusions cannot be drawn owing to a limited number of studies. Further large-scale randomized trials are required.

Fibroblast growth factor 21 alleviates acute pancreatitis via activation of the Sirt1-autophagy signalling pathway.

Fibroblast growth factor 21 (FGF21), a metabolic hormone with pleiotropic effects on glucose and lipid metabolism and insulin sensitivity, alleviates the process of acute pancreatitis (AP). However, its mechanism remains elusive. The pathological and physiological characteristics of FGF21 are observed in both patients with AP and cerulein-induced AP models, and the mechanisms of FGF21 in response to AP are investigated by evaluating the impact of autophagy in FGF21-treated mice and cultured pancreatic cells. Circulating levels of FGF21 significantly increase in both AP patients and cerulein-induced AP mice, which is accompanied by the change of pathology in pancreatic injury. Replenishment of FGF21 distinctly reverses cerulein-induced pancreatic injury and improves cerulein-induced autophagy damage in vivo and in vitro. Mechanically, FGF21 acts on pancreatic acinar cells to up-regulate Sirtuin-1 (Sirt1) expression, which in turn repairs impaired autophagy and removes damaged organs. In addition, blockage of Sirt1 accelerates cerulein-induced pancreatic injury and weakens the regulative effect in FGF21-activated autophagy in mice. These results showed that FGF21 protects against cerulein-induced AP by activation of Sirtuin-1-autophagy axis.

Prdx1 promotes the loss of primary cilia in esophageal squamous cell carcinoma.

BACKGROUND: Loss of primary cilia is frequently observed in tumor cells, suggesting that the absence of this organelle may promote tumorigenesis through aberrant signal transduction, the inability to exit the cell cycle, and promotion of tumor cell invasion. Primary cilia loss also occurs in esophageal squamous cell carcinoma (ESCC) cells, but the molecular mechanisms that explain how ESCC cells lose primary cilia remain poorly understood. METHODS: Inhibiting the expression of Prdx1 in the ESCC cells to detect the up-regulated genes related to cilium regeneration and down-regulated genes related to cilium disassembly by Gene chip. And, mice and cell experiments were carried to confirm the role of the HEF1-Aurora A-HDAC6 signaling axis in ESCC. RESULTS: In this study, we found that silencing Peroxiredoxin 1 (Prdx1) restores primary cilia formation, and over-expressing Prdx1 induces primary cilia loss in ESCC cells. We also showed that the expression of Prdx1 regulates the action of the HEF1-Aurora A-HDAC6 signaling axis to promote the disassembly of primary cilia, and suppression of Prdx1 results in decreased tumor formation and tumor mass volume in vivo. CONCLUSIONS: These results suggest that Prdx1 is a novel regulator of primary cilia formation in ESCC cells.

Pancreatic fibroblast growth factor 21 protects against type 2 diabetes in mice by promoting insulin expression and secretion in a PI3K/Akt signaling-dependent manner.

Fibroblast growth factor 21 (FGF21) is important in glucose, lipid homeostasis and insulin sensitivity. However, it remains unknown whether FGF21 is involved in insulin expression and secretion that are dysregulated in type 2 diabetes mellitus (T2DM). In this study, we found that FGF21 was down-regulated in pancreatic islets of db/db mice, a mouse model of T2DM, along with decreased insulin expression, suggesting the possible involvement of FGF21 in maintaining insulin homeostasis and islet ß-cell function. Importantly, FGF21 knockout exacerbated palmitate-induced islet ß-cell failure and suppression of glucose-stimulated insulin secretion (GSIS). Pancreatic FGF21 overexpression significantly increased insulin expression, enhanced GSIS, improved islet morphology and reduced ß-cell apoptosis in db/db mice. Mechanistically, FGF21 promoted expression of insulin gene transcription factors and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, the major regulators of insulin secretion, as well as activating phosphatidylinositol 3-kinase (PI3K)/Akt signaling in islets of db/db mice. In addition, pharmaceutical inhibition of PI3K/Akt signaling effectively suppressed FGF21-induced expression of insulin gene transcription factors and SNARE proteins, suggesting an essential role of PI3K/Akt signaling in FGF21-induced insulin expression and secretion. Taken together, our results demonstrate a protective role of pancreatic FGF21 in T2DM mice through inducing PI3K/Akt signaling-dependent insulin expression and secretion.

FGF1 improves functional recovery through inducing PRDX1 to regulate autophagy and anti-ROS after spinal cord injury.

Fibroblast growth factor 1 (FGF1) is thought to exert protective and regenerative effects on neurons following spinal cord injury (SCI), although the mechanism of these effects is not well understood. The use of FGF1 as a therapeutic agent is limited by its lack of physicochemical stability and its limited capacity to cross the blood-spinal cord barrier. Here, we demonstrated that overexpression of FGF1 in spinal cord following SCI significantly reduced tissue loss, protected neurons in the ventricornu, ameliorated pathological morphology of the lesion, dramatically improved tissue recovery via neuroprotection, and promoted axonal regeneration and remyelination both in vivo and in vivo. In addition, the autophagy and the expression levels of PRDX1 (an antioxidant protein) were induced by AAV-FGF1 in PC12 cells after H2 O2 treatment. Furthermore, the autophagy levels were not changed in PRDX1-suppressing cells that were treated by AAV-FGF1. Taken together, these results suggest that FGF1 improves functional recovery mainly through inducing PRDX1 expression to increase autophagy and anti-ROS activity after SCI.

Effect of Resourcefulness Training on Symptoms Distress of Patients with Nasopharyngeal Carcinoma.

BACKGROUND Symptom distress is very common in patients with nasopharyngeal carcinoma (NPC) during radiotherapy, seriously affecting their quality of life and impeding the process of rehabilitation. Resourcefulness training can enhance the level of resourcefulness and benefit-finding, palliate symptom distress, and promote disease rehabilitation. However, the effects of resourcefulness training on local complications and benefit-finding in NPC patients during radiotherapy remains poorly understood. MATERIAL AND METHODS Questionnaires and resourcefulness training intervention were used in this study. The relationships among resourcefulness, benefit-finding, and symptom distress of 304 NPC patients were analyzed and the effects of resourcefulness training on NPC patients (N=80) were evaluated during radiotherapy. RESULTS Among the 304 NPC patients, age, educational level, occupation, family monthly income, method of payment of medical expenses, and histological types were significant factors influencing resourcefulness and benefit-finding. The patients' resourcefulness was positively correlated to their benefit-finding; and their distress was negatively correlated to their resourcefulness. After resourcefulness training for 2 months, average scores of the resourcefulness and benefit-finding were significantly increased in the intervention group (N=40) compared to those in the control group (N=40). Average scores of symptom distress were significantly reduced in the 2 groups, but they were reduced more significantly in the intervention group than in the control group. CONCLUSIONS The patients' benefit-finding and symptom distress were correlated with their resourcefulness. Resourcefulness training could enhance the level of resourcefulness and benefit-finding, palliate symptom distress, and promote disease rehabilitation in NPC patients during radiotherapy.

CXCL16 deficiency attenuates diabetic nephropathy through decreasing oxidative stress and inflammation.

Soluble C-X-C chemokine ligand 16 (CXCL16) is related to the inflammatory response in liver injury and involved in the pathogenesis of renal dysfunction in diabetes patients. However, the exact role of elevated CXCL16 in diabetic nephropathy (DN) remains unclear. In this study, we investigated the role of CXCL16 in streptozcin (STZ)-induced diabetic nephropathy (DN) in mice. The results showed that fasting blood glucose (FBG) and 24 h urinary protein, triglyceride, and cholesterol levels increased in diabetic mice, and these changes were partially ameliorated in CXCL16 KO mice. Meanwhile, the results also showed that ROS generation was suppressed and the expression levels of inflammatory factors and infiltration factors were inhibited both in vivo and in vitro using DN models. In addition, the total AKT protein and p-AKT levels were decreased in CXCL16-depleted HK-2 cells that were treated with LPS. These findings suggest that the CXCL16 gene product promotes inflammatory factors and cell infiltration factors, and inhibits the expression of antioxidant factors to accelerate the development of DN, and CXCL16 deficiency attenuates DN may be involved in the AKT signaling pathway.

FGF21 ameliorates diabetic cardiomyopathy by activating the AMPK-paraoxonase 1 signaling axis in mice.

The aim of the present study is to explore the molecular mechanism of fibroblast growth factor 21 (FGF21) in protecting against diabetic cardiomyopathy (DCM). Streptozotocin/high-fat diet (STZ/HFD) was used to induced diabetes in FGF21-deficient mice and their wild-type littermates, followed by evaluation of the difference in DCM between the two genotypes. Primary cultured cardiomyocytes were also used to explore the potential molecular mechanism of FGF21 in the protection of high glucose (HG)-induced cardiomyocyte injury. STZ/HFD-induced cardiomyopathy was exacerbated in FGF21 knockout mice, which was accompanied by a significant reduction in cardiac AMP-activated protein kinase (AMPK) activity and paraoxonase 1 (PON1) expression. By contrast, adeno-associated virus (AAV)-mediated overexpression of FGF21 in STZ/HFD-induced diabetic mice significantly enhanced cardiac AMPK activity, PON1 expression and its biological activity, resulting in alleviated DCM. In cultured cardiomyocytes, treatment with recombinant mouse FGF21 (rmFGF21) counteracted HG-induced oxidative stress, mitochondrial dysfunction, and inflammatory responses, leading to increased AMPK activity and PON1 expression. However, these beneficial effects of FGF21 were markedly weakened by genetic blockage of AMPK or PON1. Furthermore, inactivation of AMPK also markedly blunted FGF21-induced PON1 expression but significantly increased HG-induced cytotoxicity in cardiomyocytes, the latter of which was largely reversed by adenovirus-mediated PON1 overexpression. These findings suggest that FGF21 ameliorates DCM in part by activation of the AMPK-PON1 axis.

NGF Attenuates High Glucose-Induced ER Stress, Preventing Schwann Cell Apoptosis by Activating the PI3K/Akt/GSK3ß and ERK1/2 Pathways.

Diabetic peripheral neuropathy (DPN) is one of the most common and troublesome complications of diabetes mellitus. It has been demonstrated that nerve growth factor (NGF) exerts a pivotal role in the regulation of neuronal growth and the promotion of DPN recovery. However, the exact molecular mechanisms are not well understood. Recent studies have indicated that as a novel therapeutic target, endoplasmic reticulum (ER) stress participates in the onset and progression of DPN. In the present study, it has been demonstrated that NGF prevents the sciatic nerve from degeneration and demyelination in DPN rats. Thus, RSC 96 cells, which retain the characteristic features of Schwann cells (SCs), were cultured in medium containing 30 mM glucose (high glucose, HG) to mimic SCs in DPN mice. The 50-ng/ml dose of NGF was identified to be the optimal concentration for treating an excessive ER stress level under HG conditions for 24 h. We found that NGF treatment significantly inhibits HG-induced ER stress and subsequently suppresses ER-related apoptosis. Further, NGF administration also activates the upstream signaling pathway of ER stress, PI3K/Akt/GSK3ß signaling and ERK1/2 signaling. Co-treatment with the PI3K inhibitor LY294002 or ERK1/2 inhibitor U0126 significantly reverses the protective role of NGF on HG-induced excessive ER stress and subsequent apoptosis. These observations suggest that the neuroprotective role of NGF in DPN is mediated by the inhibition of excessive ER stress via the activation of the PI3K/Akt/GSK3ß and ERK1/2 signaling pathways.

[Clinical observation of telbivudine's antiviral efficacy and protection against mother-to-infant transmission of chronic hepatitis B during the first trimester of pregnancy].

OBJECTIVE: To explore the antiviral efficacy, safety and protective ability against mother-to-infant transmission of telbivudine in pregnant patients with chronic hepatitis B (CHB) during the first trimester. METHODS: Eighty four gravid women who were diagnosed with CHB, in their first trimester of pregnancy, and had refused to terminate their pregnancies were enrolled; all study participants were clinically classified as active hepatitis cases with positivity for both hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg), HBV DNA more than or equal to 107 copies/mL and serum level of alanine aminotarnsferase (ALT) of more than or equal to 4 ULN.Patients with YMDD mutations were excluded from the study. The study participants were divided into a telbivudine treatment group (n=43; administered in the first trimester of pregnancy) and a control group (n=41, consisting of patients who refused to take antivirals). All babies bom to the women in both groups of the study received standard immune prevention (anti-hepatitis B immunoglobulin plus hepatitis B vaccine) and artificial feeding.Data recorded for the women during pregnancy included clinical findings for tests of hepatic and renal function, myocardial enzymes, blood and urine clinical parameters, hepatitis B virus makers and HBV DNA, as well as notation of any adverse reactions. The neonates were evaluated for presence of HBV infection, parameters of growth and development, presence of complications, and Apgar score. At 6 and 12 months old, all infants were evaluated for HBV DNA level and HBsAg presence. RESULTS: The genetic variant rtM204I was detected in one of the women in the treatment group at 36 weeks of pregnancy. One woman in the control group developed severe hepatitis at 28 weeks of pregnancy and was put on the telbivudine treatment The treatment group showed greater recovery rates of ALT than the control group at 12 weeks of pregnancy (62.8% vs.29.3%, P=0.002), 24 weeks of pregnancy (76.7% vs.46.3%, P=0.000), and at ante partum (88.1% vs.60.0%, P=0.004). The treatment group also showed greater HBV DNA-negative conversion rates at 12 weeks of pregnancy (20.9% vs.0, P=0.006), at 24 weeks of pregnancy (37.2% vs.0, P=0.001) and at ante partum (78.6% vs.0, P=0.000), and greater HBeAg seroconversion rates at 12 weeks of pregnancy (2.3% vs.0, P=1.000), at 24 weeks of pregnancy (9.3% vs.0, P=0.116) and at ante partum (2 1.4% vs.0, P=0.002). The HBsAg-positive rates and HBV DNA-positive rates among the infants born to the mothers in the treatment and control groups, respectively, were 2.4% vs.17.5% (P=0.027) at birth, 0 vs.17.5% (P=0.005)at 6 months old and 0 vs.17.5% (P=0.005) at 12 months old. The Apgar scores were not significantly different for the children born to the mothers from the two groups, and all the children showed parameters of growth development within normal limits. CONCLUSION: Telbivudine administration in the first trimester had a good antiviral curative effect and effectively blocked mother-to-infant transmission in women with CHB. The treatment was safe, causing no obvious adverse reaction in the gravid women or developmental effects on the infants.

Peroxiredoxin 1 is involved in disassembly of flagella and cilia.

Cilia/flagella are evolutionarily conserved cellular organelles. In this study, we demonstrated that Dunaliella salina Peroxiredoxin 1 (DsPrdx1) localized to the flagella and basal bodies, and was involved in flagellar disassembly. The link between DsPrdx1 and flagella of Dunaliella salina (D. salina) encouraged us to explore the function of its human homologue, Homo sapiens Peroxiredoxin 1 (HsPrdx1) in development and physiology. Our results showed that HsPrdx1 was overexpressed, and cilia were lost in esophageal squamous cell carcinoma (ESCC) cells compared with the non-cancerous esophageal epithelial cells Het-1A. Furthermore, when HsPrdx1 was knocked down by short hairpin RNA (shRNA) lentivirus in ESCC cells, the phenotype of cilia lost can be reversed, and the expression levels of tumor suppressor genes LKB1 and p-AMPK were increased, and the activity of the oncogene Aurora A was inhibited compared with those in cells transfected with scrambe-shRNA lentivirus. These findings firstly showed that Prdx1 is involved in disassembly of flagella and cilia, and suggested that the abnormal expression of the cilia-related gene including Prdx1 may affect both ciliogenesis and cancernogenesis.

Polygonatum cyrtonema polysaccharides reshape the gut microbiota to ameliorate dextran sodium sulfate-induced ulcerative colitis in mice.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized inflammatory imbalance, intestinal epithelial mucosal damage, and dysbiosis of the gut microbiota. Polygonatum cyrtonema polysaccharides (PCPs) can regulate gut microbiota and inflammation. Here, the different doses of PCPs were administered to dextran sodium sulfate-induced UC mice, and the effects of the whole PCPs were compared with those of the fractionated fractions PCP-1 (19.9 kDa) and PCP-2 (71.6 and 4.2 kDa). Additionally, an antibiotic cocktail was administered to UC mice to deplete the gut microbiota, and PCPs were subsequently administered to elucidate the potential role of the gut microbiota in these mice. The results revealed that PCP treatment significantly optimized the lost weight and shortened colon, restored the balance of inflammation, mitigated oxidative stress, and restored intestinal epithelial mucosal damage. And, the PCPs exhibited superior efficacy in ameliorating these symptoms compared with PCP-1 and PCP-2. However, depletion of the gut microbiota diminished the therapeutic effects of PCPs in UC mice. Furthermore, fecal transplantation from PCP-treated UC mice to new UC-afflicted mice produced therapeutic effects similar to PCP treatment. So, PCPs significantly ameliorated the symptoms, inflammation, oxidative stress, and intestinal mucosal damage in UC mice, and gut microbiota partially mediated these effects.

Early elevations of RAS protein level and activity are critical for the development of PDAC in the context of inflammation.

The KRASG12D mutation was believed to be locked in a GTP-bound form, rendering it fully active. However, recent studies have indicated that the presence of mutant KRAS alone is insufficient; it requires additional activation through inflammatory stimuli to effectively drive the development of pancreatic ductal adenocarcinoma (PDAC). It remains unclear to what extent RAS activation occurs during the development of PDAC in the context of inflammation. Here, in a mouse model with the concurrent expression of KrasG12D/+ and inflammation mediator IKK2 in pancreatic acinar cells, we showed that, compared to KRASG12D alone, the cooperative interaction between KRASG12D and IKK2 rapidly elevated both the protein level and activity of KRASG12D and NRAS in a short term. This high level was sustained throughout the rest phase of PDAC development. These results suggest that inflammation not only rapidly augments the activity but also the protein abundance, leading to an enhanced total amount of GTP-bound RAS (KRASG12D and NRAS) in the early stage. Notably, while KRASG12D could be further activated by IKK2, not all KRASG12D proteins were in the GTP-bound state. Overall, our findings suggest that although KRASG12D is not fully active in the context of inflammation, concurrent increases in both the protein level and activity of KRASG12D as well as NRAS at the early stage by inflammation contribute to the rise in total GTP-bound RAS.

Oat ß-glucan repairs the epidermal barrier by upregulating the levels of epidermal differentiation, cell-cell junctions and lipids via Dectin-1.

BACKGROUND AND PURPOSE: Oat ß-glucan could ameliorate epidermal hyperplasia and accelerate epidermal barrier repair. Dectin-1 is one of the receptors of ß-glucan and many biological functions of ß-glucan are mediated by Dectin-1. Dectin-1 promotes wound healing through regulating the proliferation and migration of skin cells. Thus, this study aimed to investigate the role of oat ß-glucan and Dectin-1 in epidermal barrier repair. EXPERIMENTAL APPROACH: To investigate the role of Dectin-1 in the epidermal barrier, indicators associated with the recovery of a damaged epidermal barrier, including histopathological changes, keratinization, proliferation, apoptosis, differentiation, cell-cell junctions and lipid content were compared between WT and Dectin-1-/- mice. Further, the effect of oat ß-glucan on the disruption of the epidermal barrier was also compared between WT and Dectin-1-/- mice. KEY RESULTS: Dectin-1 deficiency resulted in delayed recovery and marked keratinization, as well as abnormal levels of keratinocyte differentiation, cell-cell junctions and lipid synthesis during the restoration of the epidermal barrier. Oat ß-glucan significantly reduces epidermal hyperplasia, promotes epidermal differentiation, increases cell-cell junction expression, promotes lipid synthesis and ultimately accelerates the recovery of damaged epidermal barriers via Dectin-1. Oat ß-glucan could promote CaS receptor expression and activate the PPAR-γ signalling pathway via Dectin-1. CONCLUSION AND IMPLICATIONS: Oat ß-glucan promote the recovery of damaged epidermal barriers through promoting epidermal differentiation, increasing the expression of cell-cell junctions and lipid synthesis through Dectin-1. Dectin-1 deficiency delay the recovery of epidermal barriers, which indicated that Dectin-1 may be a potential target in epidermal barrier repair.