In recent years, the development of host-acting antibacterial compounds has gradually become a hotspot in the field of anti-infection. Through research on the interaction mechanism between hosts and pathogenic bacteria, it has been found that the immune system is one of the key targets of host-acting antibacterial compounds. There is a communication system called the quorum sensing system in microorganisms, which mainly adjusts the structure of multi-microbial community and coordinates the group behavior. When the quorum sensing molecules secreted by microorganisms reach a threshold concentration, the quorum sensing system is activated and the overall gene expression of the microorganism is changed. In addition to regulating the density of microorganisms, quorum sensing molecules can also act as a link between pathogenic microorganisms and hosts, entering the host immune system and playing a role in affecting the morphological structure of immune cells, secreting cytokines, and inducing apoptosis, leading to host immune injury and causing host immune dysfunction.The key mechanism of 3-oxo-C12-HSL and other acyl-homoserine lactone (AHL) molecules in the innate immune system has been extensively studied. The lipid solubility allows AHLs to pass through the plasma membrane of host immune cells easily and induce dissolution of lipid domains. Then, it acts through signaling pathways such as p38MAPK and JAK-STAT, further influencing the immune cell’s defense response to bacteria and potentially leading to cell apoptosis. Additionally, the human lactonase paraoxonase 2, which can degrade3-oxo-C12-HSL, has been found in macrophage. It acts as an immune regulator that promotes macrophage phagocytosis of pathogens and is hypothesized to have the ability to reduce bacterial resistance. The mechanism of quorum sensing molecules in the adaptive immune system is less studied, the current results suggest that 3-oxo-C12-HSL is closely related to the mitochondrial pathway in host immune cells. For example, 3-oxo-C12-HSL induces apoptosis of Jurkat cells by inhibiting the expression of three mitochondrial electron transport chain proteins; it can also trigger mitochondrial dysfunction and induce mast cell apoptosis through Ca²⁺ signaling.Among the quorum sensing molecules, the AHLs have the greatest impact on plant immune system. The different effects on plant resistance depends on the chain lengths of acyl groups in bacterial-produced AHLs. Short-chain AHLs (C4-HSL and C8-HSL) induce plant resistance to pathogenic bacteria mainly through the auxin pathway and jasmonic acid pathway. Long-chain AHL (3-oxo-C14-HSL) is commonly used in hosts against fungal pathogens by inducing stomata defense responses, and the reaction process is related to salicylic acid. Diffusible signal factor molecules also interfere with the stomatal immunity caused by pathogens. It may act through the formin nanoclustering-mediated actin assembly and MPK3 pathway to inhibit the innate immunity of Arabidopsis. In summary, AHLs induced different plant pathways and affects the plant-bacteria interactions to trigger plant immunity. As a quorum sensing molecule of fungi, farnesol has similar effects on host immunity as AHLs, such as stimulating cytokine secretion and activating an inflammatory response. It also plays a unique role on dendritic cell differentiation and maturation. In addition, studies have found that farnesol has a protective effect on autoimmune encephalomyelitis, which may be related to its effect on the composition of intestinal microorganisms of the host.Therefore, targeting the host immune system and quorum sensing molecules to develop antibacterial compounds can effectively inhibit the invasion of pathogens and subserve the host to resist the influence of pathogenic bacteria. This article will review the mechanism of host immune responses triggered by important quorum sensing molecules, aiming to explore the targets of host-acting antibacterial compounds and provide new directions for the prevention or treatment of causative infectious sources and the development of related drugs.

OBJECTIVE: Diterpenoids with a wide variety of biological activities from Anoectochilus roxburghii, a precious medicinal plant, are important active components. However, due to the lack of genetic information on the metabolic process of diterpenoids in A. roxburghii, the genes involved in the molecular regulation mechanism of diterpenoid metabolism are still unclear. This study revealed the complex metabolic genes for diterpenoids biosynthesis in different organs of A. roxburghii by combining analysis of transcriptomics and metabolomics. METHODS: The differences in diterpenoid accumulation in roots, stems and leaves of A. roxburghii were analyzed by metabonomic analysis, and its metabolic gene information was obtained by transcriptome sequencing. Then, the molecular mechanism of differential diterpenoid accumulation in different organs of A. roxburghii was analyzed from the perspective of gene expression patterns. RESULTS: A total of 296 terpenoid metabolites were identified in the five terpenoid metabolic pathways in A. roxburghii. There were 38, 34, and 18 diterpenoids with different contents between roots and leaves, between leaves and stems, and between roots and stems, respectively. Twenty-nine metabolic enzyme genes with 883 unigenes in the diterpenoid synthesis process were identified, and the DXS and FDPS in the terpenoid backbone biosynthesis stage and CPA, GA20ox, GA3ox, GA2ox, and MAS in the diterpenoid biosynthesis stage were predicted to be the key metabolic enzymes for the accumulation of diterpenoids. In addition, 14 key transcription factor coding genes were predicted to be involved in the regulation of the diterpenoid biosynthesis. The expression of genes such as GA2ox, MAS, CPA, GA20ox and GA3ox might be activated by some of the 14 transcription factors. The transcription factor NTF-Y and PRE6 were predicted to be the most important transcription factors. CONCLUSION This study determined 29 metabolic enzyme genes and predicted 14 transcription factors involved in the molecular regulation mechanism of diterpenoid metabolism in A. roxburghii, which provided a reference for the further study of the molecular regulation mechanism of the accumulation of diterpenoids in different organs of A. roxburghii.

Objective: To investigate the clinical efficacy and safety profile of hyaluronic acid dermal filler(Restylane®) in treating nasolabial folds in Chinese population. Methods: 103 subjects in this study were recruited from five Chinese clinical trial centers between July 2014 and December 2015. Subjects were treated with hyaluronic acid dermal filler in correcting nasolabial folds and an optional re-treatment was performed after 12 months according to the subjects′wishes. The improved of nasolabial folds was evaluated by the change of severity (wrinkle severity rating scale, WSRS) and aesthetic improvement (global aesthetic improvement scale, GAIS). Satisfaction of subjects on treatment was evaluated using subject satisfaction questionnaires (SSQ). Safety indicators such as pain, skin and soft tissue presentation at the injection site were continuously evaluated throughout the whole treatment process. Results: Significant improvement in scores of WSRS and GAIS of all subjects was observed after treatment. Nine months after treatment, the scores of WSRS in 80 subjects (77.7%) and GAIS in 96 subjects (93.2%) were still improved. The 68 subjects (95.8%) received re-treatment after 12 months gained further improvement in nasolabial folds. Most adverse events were mild or moderate (transient/reversible local manifestations) and all resolved before study end, no severe adverse event related to products observed. Conclusions Hyaluronic acid dermal filler is effective and safe in treatment of nasolabial folds in Chinese population and the effect can last up to 12 months.

Objective: To investigate the function of primary cilium as an oxygen sensor in PC12 cells. Methods: The PC12 cells were transfected with IFT88 siRNA. The nuclear translocation of hypoxia inducible factor-1α (HIF-1α), nuclear factor erythroid-2 related factor 2 (Nrf2), and ciliogenesis were observed by immunofluorescence staining; and the mRNA expressions of HIF-1α, Nrf2, vascular endothelial growth factor (VEGF) and superoxide dismutase (SOD) were detected by real-time RT-PCR. Results: The ciliogenesis was inhibited in PC12 cells transfected with IFT88 siRNA. In hypoxia group and scramble control group, nuclear translocations of HIF-1α and Nrf2 were observed and mRNA expressions of HIF-1α, Nrf2, VEGF were increased, and those of SOD were decreased. While in PC12 cells transfected with IFT88 siRNA, nuclear translocations of HIF-1α and Nrf2 were not observed, and mRNA expressions of HIF-1α, Nrf2, VEGF were inhibited, and mRNA expression of SOD was increased. Conclusion: Primary cilia may act as an oxygen sensor to transfer the information related to hypoxia and oxidative stress into cells, activating intracellular defense mechanism against the hypoxic injuries.
Animals ; Cilia ; metabolism ; Gene Expression Regulation ; drug effects ; Oxygen ; metabolism ; PC12 Cells ; Rats

Objective To evaluate the efficacy of intraopèrative ultrasonography (IOUS) on primary and repeated hepatectomies for hepatocellular carcinoma (HCC).Methods 430 patients underwent 555 operations for HCC.New tumors detected by IOUS at the primary and repeated hepatectomies were retrospectively analyzed.The long-term outcomes were also studied.Results IOUS had the highest sensitivity in the routinely used imaging examinations.The detection rate by each imaging modality decreased slightly but uniformly at the second hepatectomy.IOUS detected 56 new tumors in 30 patients (7.1％) at the primary hepatectomy and 13 new tumors in 8 (7.3％) at the second.The average size of tumor detected was 8.7±3.8 and 9.0±5.2 mm at the primary and second resections,respectively.The preoperative surgical plan was changed due to the IOUS findings alone in 24 patients (5.6％) at the primary hepatectomy,and in 7 (6.4％) at the second.Although recurrence was frequent in patients with new tumors detected at the primary hepatectomy,long-term survival after appropriate treatment for recurrence was similar to those patients without new tumors detected.Conlusions Despite recent progress in imaging modalities,IOUS is still the most sensitive examination.The same degree of precaution is necessary to detect new tumors using IOUS in repeated hepatectomy.Patients with new tumors detected by IOUS are at high risk for recurrence so that regular check-up is important to improve patient survival.

Objective To assess the absorbance rate of the fat after the operation of breast augmentation of the repeated injection of low volume, using ultrasonic imaging method. Methods Thirty three patients were injected with low volume of autologous fat (50-60 ml per time) to bilateral breasts for 1-5 times and breast sonographic examination was performed to evaluate the grafted fat tissues. The thickness of the retromammary fat layer before and after each injection was measured to calculate the absorbance index. Results The 264 points of breast were measured in this study. The fat was distributed in the retro-mammary fat layers at 224 points of the breast and in the pectoralis major muscle layer at 32 points of the breast, and the others distributed in the mammary gland layer.The average thickness of the retromammary fat layer increased gradually from 0.2 cm before the first operation to 1. 0 cm after the fifth operation. The average absorbance index one month after each operation was 34 %-66 %. Conclusion The present study demonstrates that breast augmentation by repeated autologous fat graft with low volume injection at each time is applicable and satisfactory and that breast ultrasound is an accurate and simple method to e-valuate the absorbance index.

Objective To evaluate the ultrasonographic (US) features and evolution of breast fat necrosis after cosmetic augmentation with autologous fat obtained by liposuction, to help distinguish fat necrosis from more ominous breast masses. Methods Breast sonography was performed on 38 patients underwent bilateral breast augmentation by autologous fat injection to evaluate the grafted fat tissues in interval of 3-6 month after the operation. Observations in follow up sonography included the sizes,positions, shape,echogenicity,margin features, calcifications and evolutions of the suspicious nodules in the breasts. Results Seventy-six nodules occurred in 25 of the 38 patients were detected after the fat graft. Among the 76 nodules,52 were cystic(68. 4%) ,8 were complex(10. 5%) and 16 were solid(21.1%). The analysis of the predominant features of the nodules sonographic appearances were as follows: all the nodules had no flow signal, 66 (86. 8%) had clear margins,54(71. 1%) had regular shapes,52 were cystic(68. 4%) ,63(82. 9% ) had no calcifications, 10(13. 2%) had egg-like calcifications,74(97. 4% ) had no halo,and the positions of the solid components in 8 complex nodules move following the change of the detected body position. There were 7 nodules with fat necrosis removed surgically and confirmed by pathology. Conclusions Breast ultrasound is an accurate and simple method to follow up the temporal changes of the fat nodules after autologous fat injection. It may help to avoid unnecessary biopsies.

OBJECTIVETo investigate the mutations of the sodium channel alpha 1 subunit gene SCN1A in severe myoclonic epilepsy of infancy (SMEI) patients and analyze its inheritance.

METHODSTwenty-three patients consistent with the diagnosis of SMEI were selected for SCN1A mutation analysis. Genomic DNA was extracted from peripheral blood lymphocytes of these patients and their parents. All the twenty-six exons of the SCN1A gene were amplified by PCR and sequenced.

RESULTSIn the 23 SMEI patients, 17 mutations were identified in 17 unrelated SMEI patients. The SCN1A mutation rate was 73.9% (17/23). The mutations included 8 missense mutations (F90S, I91T, A239T, W952G, T1210K, V1335M, V1390M and G1433E), 3 nonsense mutations (R612X, W768X and W1408X), 3 deletion mutations (A395fsX400, L556fsX557 and V1778fsX1800), 1 insertion mutation (Y1241fsX1270), 1 splice-site mutation (IVS10+3 A to G) and 1 synonymous mutation (K1492K), of which 47.1% (8/17) were truncation mutations. Thirteen mutations (F90S, I91T, T1210K, V1335M, G1433E, R612X, W768X, A395fsX400, L556fsX557, V1778fsX1800, Y1241fsX1270, IVS10+3A to G and K1492K) have not been reported previously. Except for F90S, L556fsX557 and V1778fsX1800, the other 14 mutations were de novo.

CONCLUSIONSCN1A is a major pathogenic gene for SMEI. About a half of the SCN1A mutations in SMEI cause truncation. There were no hotspots of SCN1A mutations in SMEI patients, and most mutations were de novo.

Adolescent ; Age of Onset ; Amino Acid Sequence ; Child ; Child, Preschool ; Chromosome Mapping ; Codon, Nonsense ; DNA Mutational Analysis ; Epilepsies, Myoclonic ; diagnosis ; genetics ; Exons ; genetics ; Female ; Genotype ; Humans ; Infant ; Male ; Molecular Sequence Data ; Mutation, Missense ; Nerve Tissue Proteins ; genetics ; Pedigree ; Phenotype ; Sequence Alignment ; Sequence Deletion ; Sodium Channels ; genetics

OBJECTIVETo identify the mutation of the GABA(A)-receptor gamma 2 subunit gene (GABRG2) in a Chinese family with generalized epilepsy with febrile seizures plus (GEFS+ ) and analyze the genotype-phenotype correlations and its inheritance.

METHODSGenomic DNA was extracted from peripheral blood lymphocytes of the proband and other available members in the GEFS+ family. The coding regions and flanking intronic regions of the GABRG2 gene were screened for mutations using polymerase chain reaction (PCR) and direct DNA sequencing.

RESULTSThere were 7 affected members in the three-generation family, in which one with febrile seizures (FS) and six with febrile seizures plus (FS+ ). This family was consistent with the diagnostic criteria of GEFS+ . The nonsense mutation c.1287G to A (p.W390X) in the GABRG2 gene was initially identified in the proband. Seven affected members (6 FS+ and 1 FS) and one unaffected member carried the mutation. The nonsense mutation c.1287G to A/p.W390X in the GABRG2 gene was co-segregated with the GEFS+ family. The penetrance rate was about 87.5%(7/8).

CONCLUSIONThis GEFS+ family was consistent with autosomal dominant inheritance with incomplete penetrance. GABRG2 mutation is also a disease-causing mutation in Chinese GEFS+ patients. The p.W390X mutation has not been reported previously.

Amino Acid Sequence ; Animals ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child ; Conserved Sequence ; DNA Mutational Analysis ; Epilepsy, Generalized ; complications ; genetics ; Exons ; genetics ; Genotype ; Humans ; Male ; Molecular Sequence Data ; Pedigree ; Phenotype ; Receptors, GABA-A ; chemistry ; genetics ; Seizures, Febrile ; complications ; genetics

OBJECTIVETo summarize clinical experiences in fat particle injection auto-transplantation during the past ten years.

METHODSRetrospective analysis of 334 cases of fat particle injection auto-transplantation was done, and we suggested the correct method of liposuction and fat injection.

RESULTSIn this series, one patient (0.29%) had a complication, thirty one patients (9.38%) had lower survival of autogenous fat-transplantation.

CONCLUSIONIn order to improve the results of fat-grafting, we must adopt the correct method of liposuction and follow the right rules.

Adipocytes ; transplantation ; Breast Implantation ; Face ; surgery ; Female ; Humans ; Injections ; Lipectomy ; Male ; Retrospective Studies ; Transplantation, Autologous