Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Programmed cell death 1 ligand 1 (PD-L1) is an important immunosuppressive molecule, which inhibits the function of T cells and other immune cells by binding to the receptor programmed cell death-1. The PD-L1 expression disorder plays an important role in the occurrence, development, and treatment of sepsis or other inflammatory diseases, and has become an important target for the treatment of these diseases. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with multiple differentiation potential. In recent years, MSCs have been found to have a strong immunosuppressive ability and are used to treat various inflammatory insults caused by hyperimmune diseases. Moreover, PD-L1 is deeply involved in the immunosuppressive events of MSCs and plays an important role in the treatment of various diseases. In this review, we will summarize the main regulatory mechanism of PD-L1 expression, and discuss various biological functions of PD-L1 in the immune regulation of MSCs.

Objective:To evaluate the effect of glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide receptor agonist DA-JC4 on postoperative neuroinflammatory responses in aged rats.Methods:Forty-five Sprague-Dawley rats, aged 21-23 months, weighing 530-630 g, provided by the Animal Experiment Center of Medical School of Zhengzhou University, were assigned into 3 groups ( n=15 each) using a random number table method: sham operation group (group S), operation group (group O) and DA-JC4 group (group G). Rats underwent exploratory laparotomy under anesthesia with chloral hydrate in O and G groups.In group G, DA-JC4 10 nmol/kg (dissolved in 1 ml of sterile normal saline) was intraperitoneally injected immediately after the end of operation and at 24 and 48 h after operation.Western blot was used to determine the expression of hippocampal Bax, Bcl-2, activated caspase-3, Beclin-1, microtubule-associated protein 1 light chain 3Ⅱ (LC3Ⅱ), high-mobility group box 1 protein (HMGB1), interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) on day 3 after surgery.The Morris water maze test was performed on days 14-18 after operation to assess the cognitive function. Results:Compared with group S, the escape latency was significantly prolonged on days 15-18 after operation in group O and on day 18 after operation in group G, and the number of crossing the original platform was reduced, the time spent in the target quadrant was shortened, the expression of activated caspase-3, Bax, LC3Ⅱ, HMGB1, IL-1β and TNF-α in hippocampi was up-regulated, and the expression of Bcl-2, LC3Ⅱ and Beclin-1 was down-regulated in O and G groups ( P<0.05). Compared with group O, the escape latency was significantly shortened, and the number of crossing the original platform was increased, the time spent in the target quadrant was prolonged, the expression of activated caspase-3, Bax, LC3Ⅱ, HMGB1, IL-1β and TNF-α in hippocampi was down-regulated, and the expression of Bcl-2, LC3Ⅱ and Beclin-1 was up-regulated in group G ( P<0.05). Conclusion:The mechanism by which DA-JC4 reduces postoperative cognitive dysfunction may be related to inhibiting neuroinflammatory responses in aged rats.

Objective To evaluate the effect of exercise training on heat shock protein 70 (HSP70) expression during endotoxin-induced acute lung injury (ALI) in rats.Methods Thirty-two SPF healthy male Sprague-Dawley rats,aged 8 weeks,weighing 175-220 g,were divided into 4 groups (n=8 each) using a random number table method:control group (group C),group ALI,low-intensity exercise training group (group ET1) and high-intensity exercise training group (group ET2).The rats in ET1 and ET2 groups received 2-and 4-week treadmill exercise training before establishing the ALI model,while the rats in C and ALI groups received no training.ALI was induced by intravenously injecting 5 mg/kg lipopolysaccharide via the tail vein in ALI,ET1 and ET2 groups,and the equal volume of normal saline was given instead in group C.The animals were sacrificed,and the lungs were harvested for microscopic examination of the pathological changes of lung tissues which were also scored and for determination of wet to dry weight ratio (W/D ratio),concentrations of total protein,interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in bronchoalveolar lavage fluid (BALF),and expression of HSP70 and nuclear factor kappa B (NF-κB) in lung tissues by Western blot.Results Compared with group C,the W/D ratio and pathological changes of lung tissues were significantly increased,the concentrations of total protein,IL-1 β and TNF-α in BALF were increased,the expression of NF-κB was up-regulated (P＜0.05),and no significant change was found in HSP70 expression in group ALI(P＞0.05).Compared with group ALI,the W/D ratio and pathological changes of lung tissues were significantly decreased,the concentrations of total protein,IL-1β and TNF-α in BALF were decreased,the expression of HSP70 was up-regulated,and the expression of NF-κB was down-regulated in ET1 and ET2 groups (P＜0.05).Conclusion Exercise training can attenuate the endotoxin-induced ALI through relieving the inflammatory responses,which may be related to up-regulating HSP70 expression in the lung of rats.

AIM:To investigate the effects of Jiawei-Naotai formula (JWNTF) on ATF4/CHOP/Puma pathway in hippocampal neurons of ovariectomized female rats with cerebral ischemia.METHODS:The female rats were randomly divided into sham group, model group, JWNTF group and positive control group.The rats, expect in the sham group, were ovariectomized.The rats in each group were intragastric administration 11 days after ovariectomy.The rats in sham group and model group were given a gavage of 0.9％Na Cl, while the rats in other groups were administrated by corresponding therapy intragastrically for 3 d.The regional cerebral ischemia model was established by middle cerebral artery occlusion (MCAO) suture method 14 days after ovariectomy.The behaviors of the rats were evaluated 24 h after cerebral ischemia.The mRNA levels of Bax, Bcl-2 and caspase-3 were detected by RT-qPCR, and the protein expression of Bax, Bcl-2, caspase-3, ATF4, CHOP and Puma was determined by Western blot.RESULTS:Compared with sham group, the neurobehavioral scores significantly increased in other groups (P<0.05).Compared with model group, the neurobehavioral scores were significantly decreased in positive control group and JWNTF group (P<0.05).The protein expression of Bax, caspase-3, ATF4, CHOP and Puma, and the mRNA expression of Bax and caspase-3 in the hippocampus were much higher, and Bcl-2 was lower in model group than those in sham group (P<0.05).JWNTF significantly reduced the protein expression of Bax, caspase-3, ATF4 and CHOP, and the mRNA expression of Puma, Bax and caspase-3, and markedly increased the expression of Bcl-2 at mRNA and protein levels compared with model group.CONCLUSION:The JWNTF protects against brain damage induced by cerebral ischemia, which may be related to inhibitiing the expression of ATF4/CHOP/Puma pathway-related molecules at mRNA and protein levels.

Objective To investigate diabetes-mediated changes in the neuromuscular pharmacodynamics of rocuronium in rats. Methods Diabetes mellitus was induced by a single injection of streptozotocin in rats.A total of 24 male SD rats were assigned to four groups using random number table:the normal control group,diabetic 2-week group,diabetic 4-week group,and diabetic 8-week group(6 rats per group).The sciatic nerve was stimulated in a rain-of-four(TOF)pattern,and the twitch tension changes in the tibialis anterior muscle were demonstrated by mechanomyography after intravenous injection of rocuronium in vivo.The time course characteristics of rocuronium,including onset time,and the recovery time from rocuronium injection to TOF ratio 75%(RT75%)and 90%(RT90%),were recorded,and half maximal inhibitory concentration(IC)values of rocuronium were determined using a four-parameter dose response curve. Results Compared with the normal controls,the diabetic rats had significantly prolonged onset time of rocuronium,while the RT75% and RT90% were decreased at all rocuronium doses(P<0.001).The time course changes became increasingly significant as the duration of diabetes lengthened(P<0.001).The IC and 95% confidence interval values for rocuronium in the normal control group,diabetic 2-week group,diabetic 4-week group,and diabetic 8-week group were 0.37(0.35-0.38)mg/kg,0.44(0.43-0.46)mg/kg,0.59(0.57-0.61)mg/kg,and 0.64(0.61-0.66)mg/kg,respectively.IC values were significantly higher in the diabetic groups vs.normal control(P<0.001)and gradually increased as the duration of diabetes lengthened(P<0.001).Conclusion Diabetes is associated with the rat skeletal muscle hyposensitivity to rocuronium,which is featured by prolonged onset time of rocuronium,decreased RT 75% and RT 90%,and right shift of the cumulative dose-response curve of rocuronium.
Animals ; Diabetes Mellitus, Experimental ; physiopathology ; Male ; Muscle, Skeletal ; drug effects ; Neuromuscular Nondepolarizing Agents ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Rocuronium ; pharmacology

To investigate the experience and efficacy of endoscopic thyroidectomy for papillary thyroid microcarcinoma (PTMC) through total areola approach.
 Methods: A total of 117 PTMC patients, who were diagnosed pathologically in Minimally Invasive Surgical Center, Second Xiangya Hospital, Central South University from June 2016 to December 2017, were divided into a endoscopic surgery group (n=72) and an open surgery group (n=45). The number of dissected central lymph nodes, blood loss, amount of drainage, occurrence of postoperative complication and recurrence were collected and compared.
 Results: Compared with the open surgery group, the blood loss was less and the operative time was longer in the endoscopic surgery group (P<0.05). There were no significant differences between the 2 groups in the number of dissected central lymph nodes, amount of drainage and occurrence of postoperative complication (all P>0.05). The mean follow-up time was more than 20 months, and there was no recurrence in the 2 groups. 
 Conclusion: Endoscopic thyroidectomy with central compartment neck dissection through total areola approach is safe and feasible in patients with PTMC. It has many advantages, such as no scar on neck, less blood loss, shorter hospital stay and more acceptable to young patients.
Carcinoma, Papillary ; surgery ; Endoscopy ; Humans ; Nipples ; Thyroid Neoplasms ; surgery ; Thyroidectomy

Objective To investigate the role of transient receptor potential melastatin 7(TRPM7) in sevoflurane preconditioning for inhibiting hippocampal neurons apoptosis and inflammation response induced by oxygen-glucose deprivation(OGD).Methods Fifty SD rats of postnatal 1 d were selected for extracting hippocampal neurons and randomly divided into 5 groups,including the control group(C),sevoflurane preconditioning group (Sev),OGD group,Sev preconditioningt OGD group (Sev + OGD) and Sev preconditioning+ bradykinin+OGD group(combined group).After 1.5 h oxygen-glucose deprivation,reintroduction was performed,and then the normal culture was performed again for preparing the OGD model.Hippocampal neurons in the control group were normally cultured only;which in the Sev group conducted 2 ％ Sev preconditioning for 1 h;which in the OGD group only prepared the OGD model;which in the SEv+OGD conducted 2％ Sev preconditioning for 1 h,and prepared the OGD model after 24 h;which in the combined group was simultaneously added with bradykinin(final concentration 200μmol/L) in Sev preconditioning,other treatment was same to that in the Sev+OGD group.After 24 h normal culture,the mRNA and protein levels of TRPM7,apoptosis rate,survival rate,mRNA and supernatant protein levels of IL-1β and TNF-α of the hippocampal neurons were detected.Results Compared with the control group,hippocampal neurons mRNA and protein levels of TRPM7,apoptosis rate,mRNA and supernatant protein levels of IL-1β and TNF-α in the OGD group were significantly increased(P＜0.05),whereas the survival rate was significantly decreased (P ＜ 0.05).Compared with the OGD group,hippocampal neurons mRNA and protein levels of TRPM7,apoptosis rate,mRNA and supernatant protein levels of IL-1β and TNF-α in the Sev group were significantly decreased(P＜0.05),whereas the survival rate was significantly increased(P＜0.05).Compared with the Sev group,hippocampal neurons mRNA and protein levels of TRPM7,apoptosis rate,the mRNA and supernatant protein levels of IL-1β and TNF-α in the combined group were significantly increased(P＜0.05),whereas the survival rate was significantly decreased(P＜0.05).Conclusion Sev preconditioning can attenuate hippocampal neurons apoptosis and inflammatory response after OGD via alleviating the overexpression of TRPM7.

Objective To research the monoclonal antibody KMP1 inhibited bladder cancer EJ cell lines growth and metastasis in vivo by bioluminescence imaging. Methods Immunohistochemistry was used to determine the KMP1 binding to EJ and EJ-GFP cell lines. The xenograft tumor cell growth and distribution were measured by vernier calipers and dynamic in vivo fluorescence imaging. Immunohistochemistry and H&E counterstaining researched the feature of the xenograft tumor. Results Cell growth curves of EJ and EJ-GFP cells were similar. EJ-GFP had a green fluorescence. In EJ-GFP nude mouse tumor model, the addition of KMP1 significantly inhibited tumor growth and extended the average life span of nude mice. Both EJ and EJ-GFP cells can bind to KMP1,and the weight of transplanted tumors in the KMP1 treatment group was significantly lower than that of the mIgG control group (P＜0.001).Conclusion KMP1 has a promising antitumor effect in vivo. It might be valuable for development as a promising targeted agent for bladder cancer.