Post-translational protein lactylation modification in health and diseases: a double-edged sword.

As more is learned about lactate, it acts as both a product and a substrate and functions as a shuttle system between different cell populations to provide the energy for sustaining tumor growth and proliferation. Recent discoveries of protein lactylation modification mediated by lactate play an increasingly significant role in human health (e.g., neural and osteogenic differentiation and maturation) and diseases (e.g., tumors, fibrosis and inflammation, etc.). These views are critically significant and first described in detail in this review. Hence, here, we focused on a new target, protein lactylation, which may be a "double-edged sword" of human health and diseases. The main purpose of this review was to describe how protein lactylation acts in multiple physiological and pathological processes and their potential mechanisms through an in-depth summary of preclinical in vitro and in vivo studies. Our work aims to provide new ideas for treating different diseases and accelerate translation from bench to bedside.

Transient second-degree type 2 atrioventricular block after infliximab infusion in a patient with Crohn's disease and heterozygous familial hypercholesterolemia.

Current treatments for patients in the active phase of Crohn's disease (CD) include conventional treatments and biological treatments. Infliximab (IFX), a TNF-α antagonist, is recommended to induce remission in patients with moderate-to-severe CD who have not responded to conventional therapy. IFX terminates the inflammatory cascade by inhibiting the nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), and caspase signaling pathways and increases the apoptosis of activated T cells in inflamed tissues.

Up-to-date meta-analysis of long-term evaluations of mesenchymal stem cell therapy for complex perianal fistula.

BACKGROUND: Local mesenchymal stem cell (MSC) therapy for complex perianal fistulas (PFs) has shown considerable promise. But, the long-term safety and efficacy of MSC therapy in complex PFs remain unknown. AIM: To explore the long-term effectiveness and safety of local MSC therapy for complex PFs. METHODS: Sources included the PubMed, EMBASE, and Cochrane Library databases. A standard meta-analysis was performed using RevMan 5.3. RESULTS: After screening, 6 studies met the inclusion criteria. MSC therapy was associated with an improved long-term healing rate (HR) compared with the control condition [odds ratio (OR) = 2.13; 95% confidence interval (95%CI): 1.34 to 3.38; P = 0.001]. Compared with fibrin glue (FG) therapy alone, MSC plus FG therapy was associated with an improved long-term HR (OR = 2.30; 95%CI: 1.21 to 4.36; P = 0.01). When magnetic resonance imaging was used to evaluate fistula healing, MSC therapy was found to achieve a higher long-term HR than the control treatment (OR = 2.79; 95%CI: 1.37 to 5.67; P = 0.005). There were no significant differences in long-term safety (OR = 0.77; 95%CI: 0.27 to 2.24; P = 0.64). CONCLUSION: Our study indicated that local MSC therapy promotes long-term and sustained healing of complex PFs and that this method is safe.

Insight into increased risk of portal vein thrombosis in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is one of the leading chronic liver diseases with increased morbidity and mortality rates for extrahepatic diseases (including cardiovascular disease, portal vein thrombosis, etc.). There is an increased risk of thrombosis in both the portal and systemic circulation in patients with NAFLD, independent of traditional liver cirrhosis. However, increased portal pressure, the most critical factor, is frequently observed in NAFLD patients, predisposing them to portal vein thrombosis (PVT). It has been reported that there is an 8.5% incidence of PVT among patients with non-cirrhotic NAFLD in a prospective cohort study. Based on the prothrombotic status of NAFLD itself, patients combined with cirrhosis may accelerate the development of PVT and lead to a poor prognosis. Moreover, PVT has been shown to complicate the procedure and adversely affect the outcome during liver transplantation surgery. NAFLD is in a prothrombotic state, and its underlying mechanisms have not been fully understood so far. Particularly noteworthy is that gastroenterologists currently overlook the higher risk of PVT in NAFLD. We investigate the pathogenesis of NAFLD complicated with PVT from the perspective of primary, secondary, and tertiary hemostasis, and also summarize relevant studies in humans. Some treatment options that may affect NAFLD and its PVT are also explored to improve patient-oriented outcomes.

Mechanism of anti-hyperuricemia of isobavachin based on network pharmacology and molecular docking.

BACKGROUND: Hyperuricemia is a more popular metabolic disease caused by a disorder of purine metabolism. Our previous study firstly screened out a natural product Isobavachin as anti-hyperuricemia targeted hURAT1 from a Chinese medicine Haitongpi (Cortex Erythrinae). In view of Isobavachin's diverse pharmacological activities, similar to the Tranilast (as another hURAT1 inhibitor), our study focused on its potential targets and molecular mechanisms of Isobavachin anti-hyperuricemia based on network pharmacology and molecular docking. METHODS: First of all, the putative target genes of compounds were screen out based on the public databases with different methods, such as SwissTargetPerdiction, PharmMapper and TargetNet,etc. Then the compound-pathways were obtained by the compounds' targets gene from David database for Gene Ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis. The cross pathways of compound-pathways and the diseases pathways of hyperuricemia from Comparative Toxicogenomics Database were be considered as the compound-disease pathways. Next, based on the compound-disease pathways and the PPI network, the core targets were identified based on the retrieved disease-genes. Finally, the compound-target-pathway-disease network was constructed by Cytoscape and the mechanism of isobavachin anti-hyperuricemia was discussed based on the network analysis. RESULTS: Our study demonstrated that there were five pathways involved in Isobavachin against hyperuricemia, including Drug metabolism-other enzymes, Metabolic pathways, Bile secretion, Renin-angiotensin system and Renin secretion. Among the proteins involved in these pathways, HPRT1, REN and ABCG2 were identified as the core targets associated with hyperuricemia, which regulated the five pathways mentioned above. It is quite different from that of Tranilast, which involved in the same pathways except Bile secretion instead of purine metabolism. CONCLUSION: This study revealed Isobavachin could regulate the pathways including Drug metabolism-other enzymes, Metabolic pathways, Bile secretion, Renin-angiotensin system, Renin secretion by core targets HPRT1, REN and ABCG2, in the treatment of hyperuricemia effect. Among them, the Bile secretion regulated by ABCG2 probably would be a novel pathway. Our work provided a theoretical basis for the pharmacological study of Isobavachin in lowering uric acid and further basic research.

Gut microbiota therapy for nonalcoholic fatty liver disease: Evidence from randomized clinical trials.

Nonalcoholic fatty liver disease (NAFLD) has a high prevalence worldwide, but there are no medications approved for treatment. Gut microbiota would be a novel and promising therapeutic target based on the concept of the gut-liver axis in liver disease. We reviewed randomized controlled trials on gut microbiota therapy in NAFLD in this study to evaluate its efficacy and plausibility in NAFLD.

The complete mitochondrial genome of Acanthurus mata (Acanthuriformes, Acanthuridae).

Acanthurus mata is one of most important genera of Acanthuridae. However, the systemically classification and taxonomic studies have so far been limited. In this study, we report the complete mitochondrial genome sequence of A. mata. The mitogenome has 15,102 base pairs (55.6% A + T content) and made up of total of 37 genes (13 protein-coding, 22 transfer RNAs and 2 ribosomal RNAs), and a putative control region. This study will provide useful genetic information for future phylogenetic and taxonomic classification of Acanthuridae.

A Nanoparticle-Based Hepatitis C Virus Vaccine With Enhanced Potency.

Despite the emergence of new direct-acting antivirals, hepatitis C virus (HCV) chronic infection and its consequent fibrosis and hepatocarcinoma remain a significant burden for public health, thus requiring an effective preventive vaccine. Our group previously showed that a subunit vaccine based on recombinant soluble E2 (sE2) can induce broadly neutralizing antibodies. To improve the immunogenicity of sE2, we designed and produced a fusion protein (sE2-ferritin) comprising sE2 and a ferritin unit in Drosophila S2 cells, which self-assembled into a nanoparticle with sE2 displayed on the surface. The sE2 moiety on the sE2-ferritin nanoparticle not only had nearly natural conformation but also had better affinities than the unfused sE2 to neutralizing antibodies, receptor, and patient serum. Mouse immunization studies showed that sE2-ferritin was more potent than sE2 in inducing anti-HCV broadly neutralizing antibodies. Our results demonstrate that sE2-ferritin is a vaccine candidate superior to previously developed sE2, providing a new possibility for controlling HCV.

The complete mitochondrial genome of Chaetodon wiebeli (Chaetodontiformes, Chaetodontidae).

Chaetodon wiebeli is one of the most important genera of Chaetodontidae. However, the systemic classification and taxonomic studies have so far been limited. In this study, we report the complete mitochondrial genome sequence of C. wiebeli. The mitogenome has 16,523 bp (54.3% A + T content) and is made up of a total of 37 genes (13 protein-coding, 22 transfer RNAs, and 2 ribosomal RNAs), and a putative control region. This study will provide useful genetic information for future phylogenetic and taxonomic classification of Chaetodontidae.

The complete mitochondrial genome of Thalassoma lunare (Labriformes, Labridae).

Thalassoma lunare is one of most important genera of Labridae. However, the systemically classification and taxonomic studies have so far been limited. In this study, we report the complete mitochondrial genome sequence of T. lunare. The mitogenome has 17,073 base pairs (57.7% A + T content) and made up of total of 37 genes (13 protein-coding, 22 transfer RNAs and 2 ribosomal RNAs), and a putative control region. This study will provide useful genetic information for future phylogenetic and taxonomic classification of Labridae.

[Evaluation of malaria elimination surveillance in Liyang City from 2010 to 2016].

OBJECTIVE: To evaluate the effect of malaria elimination monitoring in Liyang City, so as to provide the evidence for formulating control strategies and measures of malaria elimination. METHODS: The monitoring data about the epidemic situation, blood tests of feverish patients and epidemiology investigation of individual malaria patients in Liyang City from 2010 to 2016 were collected and analyzed by the descriptive epidemiology method. RESULTS: From 2010 to 2016, there were 67 malaria cases in total. Totally 39 196 feverish patients had blood tests for Plasmodium, and 65 of them showed positive and the positive rate was 0.17%. The other 2 cases of microscopy negative were treated with anti-malarial drugs by themselves after the onset of fever, and no Plasmodium was detected in the microscopy, but the tests with malaria rapid diagnostic kit (RDTs) were positive. Among all the 67 cases, there were 49 falciparum malaria cases, 13 ovale malaria cases and 5 vivax malaria cases. All the 67 malaria cases were imported, and the number of cases from Africa was 63 (94.03%). Totally 97.01% (65/67) of the malaria patients were male and most of them were young adults. The patients aged 30 to 49 years accounted for 73.13% (49/67) and 80.60% (54/67) of them were farmers. There were malaria cases in all the 10 towns of the city, and the time of onset had no obvious seasonal characteristics. The timely rate of case report, timely rate of blood film review, standardized treatment rate, epidemiological case investigation rate, and epidemic focus investigation and disposal rate were all 100%. There were 18 076 people with the active case investigation, but no malaria parasite positive carriers were found. The mosquito vector monitoring was performed with the methods of mosquito trap lamp and human bait half night trap, and 187 and 78 Anopheles mosquitoes were captured respectively, and all the parasites were Anopheles sinensis. A total of 88 person-times were performed for the Plasmodium examinations with microscopy and RDTs (one blood sample, two detections) in Liyang City Center for Disease Prevention and Control from 2012 to 2016, and 35 person-times were positive, including 28 person-times of Plasmodium falciparum and 7 person-times of P. ovale, and there was no statistically significant difference between the detection rates of P. falciparum, and P. ovale (adjusted χ2 = 0.05, P > 0.05). There were 34 RDTs positive cases, including 14 cases of malignant malaria, and 17 cases of malignant malaria or mixed infections of P. falciparum with other three kinds of Plasmodium parasites, and 3 cases of single infection or mixed infections of other three kinds of Plasmodium parasites, and there was a statistically significant difference among them in the positive RDTs detection rates (adjusted χ2 = 13.75, P < 0.05). CONCLUSIONS: There are still imported malaria cases and there is the risk of malaria retransmission in Liyang City. Therefore, it is necessary to strengthen the malaria surveillance work and the management of infectious sources, so as to consolidate the achievements of malaria elimination in the future.

Double Fano resonances in an individual metallic nanostructure for high sensing sensitivity.

In this paper, we report on the design and observation of double Fano resonances (DFRs) in an individual symmetry-reduced nanostructure and the induced high sensing sensitivity. Such a plasmonic nanostructure consists of a partially overlapped double-metallic nanotriangles with unequal sizes fabricated by using fast and low-cost angle-resolved nanosphere lithography. Symmetry breaking generates two narrow quadrupolar dark modes, which further enhance the coupling with fundamental bright dipole modes within the same structure, manifesting the effect of DFRs. The resonance wavelength and line shape of DFRs can be tailored by changing the degree of asymmetry as well as the size of the designed nanostructure. Based on DFRs, a high sensitivity to dielectric environment with a maximum figure of merit of 35 is measured. Due to a fast manufacturing process with high reproducibility and high structural tunability, the fabricated individual metallic nanostructure provides an opportunity for significant potential applications in localized surface plasmon resonance based single or double-wavelength sensors in the near-infrared region.

[Investigation of major parasitic diseases and related knowledge, attitude and practice among rural residents in Liyang City].

OBJECTIVE: To investigate the prevalence of major parasitic diseases and related knowledge, attitude and practice among rural residents in Liyang City, so as to provide the evidence for formulating appropriate preventive strategies and measures. METHODS: Three villages were selected from three towns as survey sites, and the residents who were above three years old and had been in the village for over six months were investigated. The Kato-Katz technique was applied to detect intestinal parasite eggs in residents' feces, and the cellophane anal swab was used to detect Enterobius vermicularis eggs among children aged 3-6 years. The iodine liquid smear and saline smear methods were used to examine intestinal protozoa cysts or trophozoites. Hookworm species were identified by the tube filter paper culture method. A structured questionnaire was used to collect the information on residents' knowledge, attitude and practice of the prevention and control of major parasitic diseases. RESULTS: Totally 759 residents were investigated and tested at the three rural survey sites, and only 2 cases were detected of parasitic infection and the total infection rate was 0.26%. Both cases were mild infections without mixed infection. The total awareness rate of knowledge on ascariasis, trichuriasis and ancylostomiasis was 37.9%, while the awareness rate of knowledge on clonorchiasis was 13.8%. The age and educational level were important factors of the knowledge on prevention and control of parasitic diseases among the residents. The formation rates of washing hands before meal and after using the toilet, and never drinking unboiled water were 83.8% and 92.1%, respectively. Totally 11.6% of the residents usually ate raw or half-cooked freshwater fishes and shrimps, and 53.0% had not the behavior to prepare raw and cooked food using the different chopping boards. The proportions of residents using fresh feces as manure and working in the field with bare feet were 13.8% and 22.8% respectively. The proportions of residents who thought they could, could not, or were not sure to change the risk behaviors and habits of parasitic infections were 40.2%, 28.5% and 31.4%, respectively. CONCLUSIONS: The infection rate of major parasitic diseases among the rural residents in Liyang City is low, and the awareness rate of knowledge on preventing parasitic diseases is also low. Therefore, the health education on the prevention and control of parasitic diseases should be strengthened to guide them to develop good hygiene, diet and farming habits. The environmental sanitation should be continuously improved to block the endemic of parasitic infection.

[Effect of ulinastatin on liver function of patients after bilateral total knee arthroplasty].

OBJECTIVE: To investigate the effect of ulinastatin, a urinary trypsin inhibitor, on the postoperative liver function in patients who have received bilateral total knee arthroplasty (TKA) under pneumatic tourniquet. METHODS: Totally 40 patients who were scheduled to receive bilateral TKA under thigh tourniquet were randomly assigned into trial group (U group, receiving intravenous ulinastatin) and control group (C group, receiving natural saline). All patients received the same general anesthesia and postoperative analgesia. The plasma concentrations of alanine transaminase (ALT), total bilirubin (TBil), and direct bilirubin (DBil) were recorded and compared preoperatively and 4, 24, 48, and 72 hours after the surgery. RESULTS: The demographic data were not significantly different between these two groups (P>0.05). The ALT was not significantly changed after the surgery in the C group (P>0.05) but was significantly decreased 48 hours (P=0.002) and 72 hours (P=0.001) after the surgery in the U group. TBil and DBil were significantly increased 48 hours (P=0.012, P=0.000) and 72 hours (P=0.000, P=0.000) after the surgery in C group, while only that at 48 hours (P=0.010, P=0.038) was significantly increased in the U group. ALT 4 hours (P=0.026), 48 hours (P=0.013), 72 hours (P=0.004) after the surgery were significantly lower in the U group than those in C group. TBil at the 72 hours postoperatively in U group was significantly lower than that in C group (P=0.036). DBil was not significantly different between C group and U group at all time points (all P>0.05). CONCLUSION: The application of ulinastatin in bilateral TKA can protect postoperative liver function.

Praeruptorin D and E attenuate lipopolysaccharide/hydrochloric acid induced acute lung injury in mice.

Acute lung injury is a life-threatening syndrome characterized by overwhelming lung inflammation and increased microvascular permeability, which causes a high mortality rate worldwide. The dry root of Peucedanum praeruptorum Dunn has been long used to treat respiratory diseases in China. In the present study, Praeruptorin A, C, D and E (PA, PC, PD and PE), four pyranocoumarins extracted from this herb, have been investigated for the pharmacological effects in experimental lung injury mouse models. In lipopolysaccharide (LPS) challenged mice, PA and PC did not show protective effect against lung injury at the dose of 80 mg/kg. However, PD and PE significantly inhibited the infiltration of activated polymorphonuclear leukocytes (PMNs) and decreased the levels of TNF-α and IL-6 in bronchoalveolar lavage fluid at the same dose. There was no statistically significant difference between PD and PE group. Further study demonstrated that PD and PE suppressed protein extravasations in bronchoalveolar lavage fluid, attenuated myeloperoxidase (MPO) activity and the pathological changes in the lung. Both PD and PE suppressed LPS induced Nuclear Factor-kappa B (NF-κB) pathway activation in the lung by decreasing the cytoplasmic loss of Inhibitor κB-α (IκB-α) protein and inhibiting the translocation of p65 from cytoplasm to nucleus. We also extended our study to acid-induced acute lung injury and found that these two compounds protected mice from hydrochloric acid (HCl)-induced lung injury by inhibiting PMNs influx, IL-6 release and protein exudation. Taken together, these results suggested that PD and PE might be useful in the therapy of lung injury.

Myrislignan attenuates lipopolysaccharide-induced inflammation reaction in murine macrophage cells through inhibition of NF-κB signalling pathway activation.

Myrislignan is a new kind of lignan isolated from Myristica fragrans Houtt. Its antiinflammatory effects have not yet been reported. In the present study, the antiinflammatory effects and the underlying mechanisms of myrislignan in lipopolysaccharide (LPS)-induced inflammation in murine RAW 264.7 macrophage cells were investigated. Myrislignan significantly inhibited LPS-induced production of nitric oxide (NO) in a dose-dependent manner. It inhibited mRNA expression and release of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α). This compound significantly inhibited mRNA and protein expressions of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) dose-dependently in LPS-stimulated macrophage cells. Further study showed that myrislignan decreased the cytoplasmic loss of inhibitor κB-α (IκB-α) protein and the translocation of NF-κB from cytoplasm to the nucleus. Our results suggest that myrislignan may exert its antiinflammatory effects in LPS-stimulated macrophages cells by inhibiting the NF-κB signalling pathway activation.

Methyl-1-hydroxy-2-naphthoate, a novel naphthol derivative, inhibits lipopolysaccharide-induced inflammatory response in macrophages via suppression of NF-κB, JNK and p38 MAPK pathways.

OBJECTIVE AND DESIGN: The anti-inflammatory effect of methyl-1-hydroxy-2-naphthoate (MHNA), a novel naphthol derivative, was evaluated in the lipopolysaccharide (LPS)-induced inflammatory response in murine macrophages. MATERIALS AND METHODS: The release of nitric oxide (NO), interleukin-1beta (IL-1ß) and interleukin-6 (IL-6) were detected by the Griess reagent and ELISA methods. The protein expressions of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) were examined by Western blotting. The mRNA expressions of IL-1ß, IL-6, iNOS and COX-2 were determined by real-time PCR. Activation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) pathways were detected by Western blotting, reporter gene assay and electrophoretic mobility shift assay. RESULTS: MHNA significantly inhibited the release of NO, IL-1ß and IL-6 as well as the protein expression of iNOS and COX-2 in LPS-stimulated macrophages. It also inhibited the mRNA expression of iNOS, COX-2, IL-1ß and IL-6. Further studies indicated that MHNA inhibited LPS-induced increases in NF-κB DNA-binding activity and NF-κB transcriptional activity as well as IκB-α degradation and NF-κB translocation in a dose-dependent manner. Meanwhile, the activation of p38 MAPK and c-Jun N-terminal kinases (JNK) induced by LPS were decreased by MHNA. CONCLUSIONS: MHNA inhibits the LPS-induced inflammatory response in murine macrophages via suppression of NF-κB and MAPKs signaling pathways activation.

[Comparison of the influences of continuous femoral nerve block and patient controlled intravenous analgesia on total knee arthroplasty].

OBJECTIVE: To assess the influences of continuous femoral nerve block (CFNB) and patient-controlled intravenous analgesia (PCIA) on postoperative pain scores,knee rehabilitation,and stress response after total knee arthroplasty (TKA). METHODS: Totally 32 adult patients scheduled for elective total knee arthroplasty were equally randomized into CFNB group or PCIA group. Intraoperative hemodynamics and fentanyl dose were recorded. Pain was assessed at rest and during continuous passive motion (CPM) using a visual analog scale at post-anesthesia care unit (PACU) and 4, 8, 12, 24, and 48 hours postoperatively. Morphine consumption was also recorded. As indicators of stress and inflammatory response,the leukocyte count, serum lactic acid, blood glucose, serum C-reactive protein (CRP), and serum cortisol were determined on admission, to operation room, immediately after skin incision, before extubation,on post-operation day 1 (POD1), and on POD2. RESULTS: CFNB group showed significantly lower heart rate compared with PCIA group 60 minutes and 90 minutes intraoperatively (Pü0.05). Intraoperative consumption of fentanyl was significantly lower in CFNB group (137.5∓44.4) µg than in PCIA group (264.1∓67.1) µg (Pü0.01). The CFNB group showed significantly lower VAS scores both at rest and during CPM compared with PCIA group at all time points (Pü0.05). Morphine consumption was significantly lower in CFNB group than in PCIA group at different time points (Pü0.05 or Pü0.01). The maximal continuous passive motion amplitude of CFNB group were significantly larger than that of PCIA group on POD1 [(55.0∓9.4) vs.(44.6∓9.9), P[(76.3∓11.0) vs. (67.5∓10.3), P<0.05]. The incidences of somnolence and nausea/vomiting in CFNB group were 37.5% and 37.5%, respectively,which were significantly lower than those of PCIA group (75.0% and 81.3%) (Pü0.05). Patient satisfaction scores on anesthesia and post-operative analgesia was significantly higher in CFNB group than in PCIA group (93.1∓7.9 vs. 79.1∓11.9, respectively) (Pü0.05). CONCLUSION: After TKA,CFNB technique provides more stable intraoperative hemodynamics than PCIA, with better pain relief,faster postoperative knee rehabilitation,less side effects,and higher patient satisfaction.