SIRT1 improves lactate homeostasis in the brain to alleviate parkinsonism via deacetylation and inhibition of PKM2.

Sirtuin 1 (SIRT1) is a histone deacetylase and plays diverse functions in various physiological events, from development to lifespan regulation. Here, in Parkinson's disease (PD) model mice, we demonstrated that SIRT1 ameliorates parkinsonism, while SIRT1 knockdown further aggravates PD phenotypes. Mechanistically, SIRT1 interacts with and deacetylates pyruvate kinase M2 (PKM2) at K135 and K206, thus leading to reduced PKM2 enzyme activity and lactate production, which eventually results in decreased glial activation in the brain. Administration of lactate in the brain recapitulates PD-like phenotypes. Furthermore, increased expression of PKM2 worsens PD symptoms, and, on the contrary, inhibition of PKM2 by shikonin or PKM2-IN-1 alleviates parkinsonism in mice. Collectively, our data indicate that excessive lactate in the brain might be involved in the progression of PD. By improving lactate homeostasis, SIRT1, together with PKM2, are likely drug targets for developing agents for the treatment of neurodegeneration in PD.

Identification of an m6A Natural Inhibitor, Lobeline, That Reverses Lenvatinib Resistance in Hepatocellular Tumors.

Hepatocellular carcinoma (HCC) is an aggressive cancer that has an effect on human health. As a first-line drug for HCC, despite its excellent efficacy, lenvatinib (Len) is prone to developing drug resistance in HCC patients. The N6-methyladenosine (m6A) modification is not only related to the development of HCC but also shows great potential in overcoming HCC resistance. Using Dot Blot, our group first screened a small molecule m6A regulator, lobeline (Lob), from a library of 390 compounds (mostly natural products). In vitro experiments demonstrated that Lob could significantly enhance the sensitivity to Len of Len-resistant HCC (HCC/Len) and inhibit migration of resistant cells. In Len-resistant cell-derived and patient-derived xenograft models, Lob could reverse the resistant phenotype, with reductions in tumor volume of 68% and 60%, respectively. Furthermore, MeRIP-m6A sequencing results indicated that the underlying molecular mechanism of Lob reversal of HCC drug resistance was related to UBE3B. Taken together, this study highlighted that Lob, a plant derived natural product, could reverse the resistance of HCC to Len by regulating the m6A levels. It is hoped that this will provide a pharmacological research basis for the clinical treatment of HCC patients.

A case report of using gauze packing to treat postoperative chest bleeding after left pneumonectomy for secondary rifampicin-resistant tuberculosis.

One patient with rifampin-resistant tuberculosis underwent emergency left pneumonectomy and thoracic gauze packing for hemoptysis due to recurrent hemoptysis after transcatheter arterial embolization. Vital signs were maintained by mechanical ventilation and medication. Tracheotomy and anti-tuberculosis treatment were performed. After half a year of follow-up, the patient's condition was stable.

RNAi screens identify HES4 as a regulator of redox balance supporting pyrimidine synthesis and tumor growth.

NADH/NAD+ redox balance is pivotal for cellular metabolism. Systematic identification of NAD(H) redox regulators, although currently lacking, would help uncover unknown effectors critically implicated in the coordination of growth metabolism. In this study, we performed a genome-scale RNA interference (RNAi) screen to globally survey the genes involved in redox modulation and identified the HES family bHLH transcription factor HES4 as a negative regulator of NADH/NAD+ ratio. Functionally, HES4 is shown to be crucial for maintaining mitochondrial electron transport chain (ETC) activity and pyrimidine synthesis. More specifically, HES4 directly represses transcription of SLC44A2 and SDS, thereby inhibiting mitochondrial choline oxidation and cytosolic serine deamination, respectively, which, in turn, ensures coenzyme Q reduction capacity for DHODH-mediated UMP synthesis and serine-derived dTMP production. Accordingly, inhibition of choline oxidation preserves mitochondrial serine catabolism and ETC-coupled redox balance. Furthermore, HES4 protein stability is enhanced under EGFR activation, and increased HES4 levels facilitate EGFR-driven tumor growth and predict poor prognosis of lung adenocarcinoma. These findings illustrate an unidentified mechanism, underlying pyrimidine biosynthesis in the intersection between serine and choline catabolism, and underscore the physiological importance of HES4 in tumor metabolism.

Osteocytes/Osteoblasts Produce SAA3 to Regulate Hepatic Metabolism of Cholesterol.

Hypercholesterolaemia is a systemic metabolic disease, but the role of organs other than liver in cholesterol metabolism is unappreciated. The phenotypic characterization of the Tsc1Dmp1 mice reveal that genetic depletion of tuberous sclerosis complex 1 (TSC1) in osteocytes/osteoblasts (Dmp1-Cre) triggers progressive increase in serum cholesterol level. The resulting cholesterol metabolic dysregulation is shown to be associated with upregulation and elevation of serum amyloid A3 (SAA3), a lipid metabolism related factor, in the bone and serum respectively. SAA3, elicited from the bone, bound to toll-like receptor 4 (TLR4) on hepatocytes to phosphorylate c-Jun, and caused impeded conversion of cholesterol to bile acids via suppression on cholesterol 7 α-hydroxylase (Cyp7a1) expression. Ablation of Saa3 in Tsc1Dmp1 mice prevented the CYP7A1 reduction in liver and cholesterol elevation in serum. These results expand the understanding of bone function and hepatic regulation of cholesterol metabolism and uncover a potential therapeutic use of pharmacological modulation of SAA3 in hypercholesterolaemia.

Transcriptome analysis reveals key genes and pathways for prickle development in Zanthoxylumarmatum.

Zanthoxylum armatum is an economically important tree species. However, well-developed prickles on its stems and leaves pose serious challenges in terms of management and harvesting. To investigate the molecular mechanism underlying prickle development, we sequenced different stages of prickle morphological development and transcriptomes of different tissues in the root tips (Gen), leaf buds (Ya), and fruits of Z. armatum. The results revealed that proteins related to cell division and genes related to the growth hormone signaling pathway were highly expressed in the prickle just protrusion (PC1). In addition, a high expression of lignin biosynthesis genes was observed during the developmental onset of lignification (PC2) and prickle lignification (PC3). These findings indicate that phenylpropanoid biosynthesis and plant hormone signal transduction are key pathways for the completion of lignification development in the prickle. During prickle development, ZaMYB2 and ZaWRKY3 were significantly upregulated in PC2 and PC3, suggesting their possible involvement in prickle development. Transcriptome and qRT-PCR analyses revealed differential gene expression of zaPAL3, za4CLL1, zaCOMT1, ZaWRKY3, and ZaCCD31 in the Gen, Ya, newly formed fruit (ZaF1), newly oil-spotted fruits (ZaF2), PC1, PC2, and PC3 of Zarmatum. zaCCD31 was highly expressed in leaf buds, whereas Za4CLL1 was highly expressed in root tips. During the lignification of prickles, the relative expression of genes including zaMYB2 increased gradually; however, the relative expression of zaCCD31 decreased during this process. Therefore, we inferred that these genes might be closely related to prickle development. Notably, zaMYB2 was expressed at higher levels in PC2 and PC3 than in PC1 and was not expressed in Gen, Ya, ZaF1, and ZaF2. Therefore, zaMYB2 is a key gene involved in prickle development of Z. armatum that exhibited tissue-specific expression. This study establishes a foundation for future analyses of the molecular mechanism underlying prickle development in Z. armatum.

Application of transumbilical single port laparoscopic surgery for adnexal masses in pregnancy.

OBJECTIVE: To evaluate the safety and feasibility of single-port laparoscopy during pregnancy in short term and long term. METHODS: A multicenter retrospective study was conducted to investigate the clinical data of 38 pregnant women with adnexal masses who underwent transumbilical single-port laparoscopic surgery from January 2017 to March 10, 2023. RESULTS: The mean operation time was 72.7 ± 29.6 (30-160) min. The mean intraoperative blood loss was 30.5 ± 80.4 mL, the mean postoperative first defecation time was 2.5 ± 0.7 days, and the mean total hospital stay was 6.9 ± 1.4 days. None of the patients used analgesic drugs postoperatively. Two patients developed missed abortions within 1 month of surgery, one underwent induction of labor due to a dead fetus at 24 weeks and 5 days of gestation, and the other patients did not develop adverse events after surgery. Mean birth weight was 3322.3 ± 396.3 g. The fetal heart rate was 139 ± 6.4 bpm before operation and 149 ± 2.7 bpm after operation. The APGAR score at 1 and 10 min was 9.2 ± 0.6 points and 9.9 ± 0.2 points, respectively. The mean follow-up time was 23.9 ± 16.1 (4.7-56) months, 90% (27/30) of the children had moderate developmental quotient, and 10% (3/30) of the children had good developmental quotient, without borderline low developmental quotient or mental retardation. CONCLUSION: It is safe, practical, and worthwhile to promote transumbilical single port laparoscopic surgery for pregnancies with adnexal masses in both short and long term.

Is it possible for fulvic acid modified dredged sediment biochar to adsorb tetracycline and result in a novel method of resource utilization?

In this study, dredged sediment from Baiyang Lake was used as raw material to prepare DSB at a pyrolysis temperature of 600 °C and in an anoxic pyrolysis atmosphere. The adsorption and removal performance of tetracycline in water of DSB were investigated using fulvic acid (FA) as the activator. The biochar materials were first characterized (SEM, BET, XRD, FTIR, and XPS), and the elemental composition and surface functional groups of F-DSB were investigated. The maximum adsorption capacity of F-DSB, according to the Langmuir model, was 72.3 mg/g. Results demonstrated that F-DSB exhibited good adsorption performance. In conclusion, FA is a potential green modifier that can be used to improve the adsorption properties of DSB. This research will be useful in improving our understanding of the possible adsorption mechanism and process optimization of modified DSB. This work offers a novel approach to the resource utilization of dredged sediment.

The safety and efficacy of decortication for stage III drug-resistant tuberculous empyema.

OBJECTIVES: The goal of this study was to evaluate the safety and efficacy of decortication for stage III drug-resistant tuberculous empyema (TE). METHODS: We analysed all patients with stage III TE who underwent decortication between March 2015 and October 2019 at Wuhan Pulmonary Hospital. The patients were divided into 2 groups according to drug-susceptibility testing of bronchoscopy lavage fluid, pleural effusion and tissue specimens, including a drug-resistant group and a drug-sensitive group. We collected and compared the preoperative, perioperative and postoperative data from the 2 groups to evaluate the safety and efficacy of decortication for stage III drug-resistant TE. RESULTS: In total, 135 cases met the inclusion criteria and were enrolled, including 30 cases in the drug-resistant group and 105 cases in the drug-sensitive group. No deaths were recorded for the entire study population. Compared to the drug-sensitive group, the drug-resistant group had longer operation times (259.8 ± 78.4 min vs 187.2 ± 56.0 min, P = 0.00), a larger volume of intraoperative blood loss [300 (200,400) ml vs 200 (130, 300) ml, P = 0.00] and a higher intraoperative transfusion rate (5/30, 16.7% vs 4/105, 3.8%, P = 0.04). The rate of complications was significantly higher in the drug-resistant group (23; 76.7%) than in the drug-sensitive group (53; 50.5%) (P = 0.01). Recurrence was not reported in any of the patients. Twenty-three (76.7%) patients in the drug-resistant group and 90 (85.7%) patients in the drug-sensitive group recovered to an "excellent" level, and 3 cases in each group recovered to a "poor" level; there was no significant difference between the 2 groups in surgical effects (P = 0.21). CONCLUSIONS: Decortication is a safe, effective and feasible option for patients with stage III drug-resistant TE, although the operation is difficult and risky.

IGF1R-phosphorylated PYCR1 facilitates ELK4 transcriptional activity and sustains tumor growth under hypoxia.

The proline synthesis is importantly involved in tumor growth under hypoxia, while the underlying mechanism remains to be further investigated. Here we show that pyrroline-5-carpoxylate reductase-1 (PYCR1), displaying a constant nuclear localization, is phosphorylated by nuclear IGF1R at Tyrosine 135 under hypoxia; this phosphorylation promotes the binding of PYCR1 to ELK4 and thus PYCR1 recruitment to ELK4-targeted genes promoter. Under hypoxia, ELK4-binding ability and enzymatic activity of PYCR1 are both required for ELK4-Sirt7-mediated transcriptional repression and cell growth maintenance, in which PYCR1-catalyzed NAD+ production stimulates the deacetylation activity of Sirt7 on H3K18ac that restrains genes transcription. Functionally, PYCR1 Tyr-135 phosphorylation exerts supportive effect on tumor growth under hypoxia, and the level of PYCR1 Tyr-135 phosphorylation is associated with malignancy of colorectal cancer (CRC). These data uncover the relationship between the compartmentally metabolic activity of PYCR1 and genes transcription regulation, and highlight the oncogenic role of PYCR1 during CRC development.

Feasibility and safety of uniportal thoracoscopy for chronic pulmonary aspergillosis.

Surgery plays a crucial role in the treatment of patients with chronic pulmonary aspergillosis (CPA). However, there is currently limited information available regarding the use of uniportal thoracoscopy (Uni-VATS) in CPA patients. To address this gap, we conducted a retrospective analysis of surgical procedures performed at a single center, aiming to demonstrate the feasibility and safety of Uni-VATS for patients with CPA. We collected basic information and surgical data from patients who underwent surgery for CPA at our hospital between January 2018 and June 2022. All patients received voriconazole antifungal medication for 3-6 months post-surgery and were monitored for a minimum of 6 months. A total of 110 patients, comprising 59 cases in the traditional open chest incision group and 51 cases in the Uni-VATS group, met the inclusion criteria. Among those who underwent surgery, 70% were male (77/110). The median age (IQR) of all enrolled patients was 55 (46-62) years. There were no statistically significant differences in general information, such as age, sex, comorbidities, BMI, FEV1, FVC, clinical symptoms, location of the disease, and duration of voriconazole antifungal medication, between the OS group and the Uni-VATS group (p > 0.05). The postoperative complication rates were 40.7% (24/59) for the traditional open chest incision group and 17.6% (9/51) for the Uni-VATS group. Through univariate analysis, we identified sex and operative approach as risk factors for postoperative complications. Multivariate logistic analysis confirmed that male and OS procedures were the independent risk factors for postoperative complications. There were statistically significant differences in operative time, intraoperative blood loss volume, postoperative drainage volume, pain scores, postoperative drainage tube removal time, postoperative hospital stay time between the OS group and the Uni-VATS group (p < 0.05). Uni-VATS is a feasible and safe surgical procedure for patients with CPA, and we recommend it as a preferred option for selected patients with CPA.

Open decortication for patients presenting with stage III tuberculous empyema with low density lines on CT imaging.

To explore the influence of CT findings on the optimal timing of open decorticationin patients with stage III tuberculous empyema. A total of 80 patients with stage III tuberculous empyema who had undergone open decortications were recruited; 44 patients had chest CT findings indicating low-density lines, while 36 patients did not show this imaging finding. Demographic data, perioperative data and preoperative and postoperative chest CT images were collected. In the low-density line group, the duration of disease (P = 0.0030) and the preoperative anti-tuberculosis time (P = 0.0016) were longer than those of the group without low-density lines, and the ESR (P = 0.0218), CRP (P = 0.0027) and leukocyte count (P = 0.0339) were lower in the low-density line group. Additionally, in the median operative time (P = 0.0003), intraoperative blood loss (P < 0.0001), volume of catheter drainage during 48 h after operation (P = 0.0067), chest tube duration (P < 0.0001), and length of hospital stay (P = 0.0154) were significantly lower in the low-density line group than in the group without low-density lines. A total of 88.64% of participants in the low-density line group showed hyperplasia with hyaline degeneration in pathological examination, which was observed only in 41.67% of patients without low-density lines. In addition, gaseous necrosis was considerably higher in patients without a low-density line (P = 0.004), while the low-density line group had a higher rate of treatment success (P < 0.05). Patients with stage III tuberculous empyema presenting with low-density lines around the thickened fibrous pleural rind on preoperative CT imaging may be good candidates for open decortication.

Is VATS suitable for lung diseases with hemoptysis? Experience from a hemoptysis treatment center in China.

BACKGROUND: Surgery is crucial in the treatment of the potentially fatal pulmonary hemoptysis condition. Currently, most patients with hemoptysis are treated by traditional open surgery (OS). To illustrate the effectiveness of video-assisted thoracic surgery (VATS) for hemoptysis, we developed a retrospective study of surgical interventions for lung disease with hemoptysis. METHODS: We collected and then analysed the data, including general information and post-operative outcomes, from 102 patients who underwent surgery for a variety of lung diseases with hemoptysis in our hospital between December 2018 and June 2022. RESULTS: Sixty three cases underwent VATS and 39 cases underwent OS. 76.5% of patients were male (78/102). Comorbidities with diabetes and hypertension were 16.7% (17/102) and 15.7% (16/102) respectively. The diagnoses based on postoperative pathology included aspergilloma in 63 cases (61.8%), tuberculosis in 38 cases (37.4%) and bronchiectasis in 1 case (0.8%). 8 patients underwent wedge resection, 12 patients underwent segmentectomy, 73 patients underwent lobectomy and 9 patients underwent pneumonectomy. There were 23 cases of postoperative complications, of which 7 (30.4%) were in the VATS group, significantly fewer than 16 (69.6%) in the OS group (p = 0.001). The OS procedure was identified as the only independent risk factor for postoperative complications. The median (IQR) of postoperative drainage volume in the first 24 h was 400 (195-665) ml, which was 250 (130-500) ml of the VATS group, significantly less than the 550 (460-820) ml of the OS group (p < 0.05). The median (IQR) of pain scores 24 h after surgery was 5 (4-9). The median (IQR) of postoperative drainage tube removal time was 9.5 (6-17) days for all patients, and it was 7 (5-14) days for the VATS group, which was less than 15 (9-20) days for the OS group. CONCLUSION: VATS for patients with lung disease presenting with hemoptysis is an effective and safe option that may be preferred when the hemoptysis is uncomplicated and the patient's vital signs are stable.

Successful surgical treatment of bronchopleural fistula caused by severe pulmonary tuberculosis: A case report and review of literature.

BACKGROUND: Bronchopleural fistula (BPF) is a relatively rare, but severe complication of pulmonary tuberculosis. It is associated with significant mortality; however, its management remains a major therapeutic challenge. CASE SUMMARY: We present a 24-year-old man with BPF resulting from severe pulmonary tuberculosis combined with mixed infections. The damaged right upper lobe and concomitant empyema were demonstrated via computed tomography. After undergoing open-window thoracostomy and tuberculosis treatment for 4 mo, decortication and right upper lobectomy were subsequently performed, leading to the resolution of tuberculosis and other concurrent pulmonary infections. Follow-up, 6 mo after surgery, failed to reveal any evidence of infection recurrence resulting in a good prognosis. CONCLUSION: The disease course of tuberculous BPF is particularly challenging. Surgical intervention serves as an effective and safe therapeutic strategy for BPF.

Patterns of Chromosomal Variation, Homoeologous Exchange, and Their Relationship with Genomic Features in Early Generations of a Synthetic Rice Segmental Allotetraploid.

Polyploidization is a driving force in plant evolution. Chromosomal variation often occurs at early generations following polyploid formation due to meiotic pairing irregularity that may compromise segregation fidelity and cause homoeologous exchange (HE). The trends of chromosomal variation and especially factors affecting HE remain to be fully deciphered. Here, by whole-genome resequencing, we performed nuanced analyses of patterns of chromosomal number variation and explored genomic features that affect HE in two early generations of a synthetic rice segmental allotetraploid. We found a wide occurrence of whole-chromosome aneuploidy and, to a lesser extent, also large segment gains/losses in both generations (S2 and S4) of the tetraploids. However, while the number of chromosome gains was similar between S2 and S4, that of losses in S4 was lower than in S2. HEs were abundant across all chromosomes in both generations and showed variable correlations with different genomic features at chromosomal and/or local scales. Contents of genes and transposable elements (TEs) were positively and negatively correlated with HE frequencies, respectively. By dissecting TEs into different classes, retrotransposons were found to be negatively correlated with HE frequency to a stronger extent than DNA transposons, whereas miniature terminal inverted elements (MITEs) showed a strong positive correlation. Local HE frequencies in the tetraploids and homologous recombination (HR) rates in diploids within 1 Mb sliding windows were significantly correlated with each other and showed similar overall distribution profiles. Nonetheless, non-concordant trends between HE and HR rates were found at distal regions in some chromosomes. At local scale, both shared and polymorphic retrotransposons between parents were negatively correlated with HE frequency; in contrast, both shared and polymorphic MITEs showed positive correlations with HE frequency. Our results shed new light on the patterns of chromosomal number variation and reveal genomic features influencing HE frequency in early generations following plant polyploidization.

The negative effect of G1958A polymorphism on MTHFD1 protein stability and HCC growth.

PURPOSE: Methylenetetrahydrofolate dehydrogenase (MTHFD1), a key enzyme on the folate pathway, has been implicated in the tumor development of distinct types of cancers. The single nucleotide polymorphism (SNP) of 1958G > A mutation in the coding region of MTHFD1 (arginine 653 is mutated into glutamine) has been detected in a significant proportion of clinical samples of hepatocellular carcinoma (HCC). METHODS : Hepatoma cell lines, 97H and Hep3B were used. The expression of MTHFD1 and SNP mutation protein was determined by immunoblotting analysis. The protein ubiquitination of MTHFD1 was detected by immunoprecipitation analysis. The post-translational modification sites and interacting proteins of MTHFD1 in the presence of G1958A SNP were identified by mass spectrometry. Metabolic flux analysis was used to detect the synthesis of relevant metabolites sourced from serine isotope. RESULTS: The present study showed G1958A SNP of MTHFD1, encoding MTHFD1 R653Q, was associated with the attenuated protein stability caused by ubiquitination-mediated protein degradation. Mechanistically, MTHFD1 R653Q displayed an enhanced binding to the E3 ligase TRIM21, which was responsible for the augmented ubiquitination, and MTHFD1 K504 was identified to be the primary ubiquitination site. The subsequent metabolite analysis revealed MTHFD1 R653Q resulted in the repressed flux of serine-derived methyl group into metabolite precursors for purine synthesis, and the compromised purine synthesis was demonstrated to be responsible for the impeded growth capability in MTHFD1 R653Q-expressing cells. Moreover, the suppressive effect of MTHFD1 R653Q expression in tumorigenesis was verified by xenograft analysis, and the relationship between MTHFD1 G1958A SNP and its protein levels was revealed in clinical human liver cancer specimens. CONCLUSION: Our results uncovered an unidentified mechanism underlying of the impact of G1958A SNP on MTHFD1 protein stability and tumor metabolism in HCC. which provides a molecular basis for the according clinical management when considering MTHFD1 as a therapeutic target.

Structured electroplating sludge derived membrane for one-step removal of oil, metal ions, and anions from oil/water emulsions.

The effective simultaneous treatment of hazardous waste sludge and complex oil/water emulsions in one way is urgently desired but still a challenging issue. Herein, this work for the first time presents a green and efficient strategy to fabricate an electroplating sludge (ES) derived multifunctional self-supporting membrane for the one-step removal of emulsified oils, soluble metal ions, and anions in complex oily wastewater. Due to low cost of ES and sustainability of the solvent selected in fabrication process, the large-scale application of the membrane is easily to promote. The assembled hierarchical nanostructure endowed robust underwater superoleophobicity of the membrane even under various corrosive aqueous environments, as well as excellent ultra-low oil adhesion and anti-oil-fouling performance, without chemical modification. Significantly, the multifunctional membrane possessed desirable simultaneous separation efficiency for five typical oil-in-water emulsions (>99.4%, high oil/water selective wettability), including crude oil-in-water emulsion with high viscosity (>99.6%), Cu2+ (>96.1%, surface complexation and ionic exchange), and Cl- (>92.7%, electrostatic attraction). Therefore, this green, low-cost, and multifunctional membrane not only allows the large-scale resource utilization of hazardous waste sludge, but also effectively solves the problems of complex oily wastewater purification.

Chitosan Lactate Particles for Non-Compression Hemostasis on Hepatic Resection.

The liver is the most complex vascular anatomy of all human organs, with extremely rich blood flow and fragile texture. Massive liver bleeding usually occurs after traumatic liver injury, causing severe systematic issues. Thus, bleeding control is critical in hindering mortality rates and complications in patients. In this study, non-compression hemostasis materials based on chitosan lactate particles (CLP) were developed for handling liver bleeding after injuries. CLP showed good blood biocompatibility and antibacterial performance against S. aureus. Taking advantage of the vital capacity of CLP to promote red blood cell and platelet adhesion, CLP exhibited in vivo homeostasis properties as non-compression hemostasis materials for traumatic liver injury, both in SD rats, New Zealand rabbits, or in beagles. Whereas CLP has better hemostasis than the commercial hemostatic agent Celox™.

Cordycepin Protects against Hepatic Ischemia/Reperfusion Injury via Inhibiting MAPK/NF-κB Pathway.

Hepatic ischemia/reperfusion injury (HIRI) is a common complication of liver surgery requiring hepatic disconnection, such as hepatectomy and liver transplantation. The aim of this study was to investigate the effects of cordycepin on HIRI and to elucidate the underlying mechanisms. Balb/c mice were randomly divided into six groups: a normal control group, sham group, H-cordycepin group, HIRI group, L-cordycepin (25 mg/kg) + HIRI group, and H-cordycepin (50 mg/kg) + HIRI group. Mice were subjected to I/R, and cordycepin was intragastrically administered for seven consecutive days before surgery. Orbital blood and liver specimens were collected at 6 and 24 h after HIRI. Serum levels of ALT and AST were decreased in the cordycepin pretreatment groups. Notably, cordycepin attenuated the inflammatory response and the production of proapoptosis proteins, while increasing expression of antiapoptosis proteins and decreasing expression of autophagy-linked proteins. Furthermore, cordycepin inhibited activation of the MAPK/NF-κB signaling pathway. Collectively, these results indicate that cordycepin pretreatment ameliorated hepatocyte injury caused by HIRI. As compared with the HIRI group, cordycepin pretreatment mitigated the inflammatory response and inhibited apoptosis and autophagy via regulation of the MAPK/NF-κB signaling pathway.

The success of biomaterial-based tissue engineering strategies for peripheral nerve regeneration.

Peripheral nerve injury is a clinically common injury that causes sensory dysfunction and locomotor system degeneration, which seriously affects the quality of the patients' daily life. Long gapped defects in large nerve are difficult to repair via surgery and limited donor source of autologous nerve greatly challenges the successful nerve repair by transplantation. Significantly, remarkable progress has been made in repairing the peripheral nerve injury using artificial nerve grafts and a variety of products for peripheral nerve repair have emerged been approved globally in recent years. The raw materials of these commercial products includes natural/synthetic polymers, extracellular matrix. Despite a lot of effort, the desirable functional recovery still remains great challenges in long gapped nerve defects. Thus this review discusses the recent development of tissue engineering products for peripheral nerve repair and the design of bionic grafts improving the local microenvironment for accelerating nerve regeneration against locomotor disorder, which may provide potential strategies for the repair of long gaps or thick nerve defects by multifunctional biomaterials.