Current trends and advances of Quorum sensing inhibitors and their biotechnological applications

Serious setbacks were witnessed in shrimp farming, the food industry, and the ship industry during the past three decades primarily due to bacterial pathogens that coordinate by quorum sensing (QS). The influence of bacterial pathogens utilizing QS. The impact of QS cell communication on public health is extremely disastrous in terms of spread, spectrum, apart from their economic impact. The overuse of antibiotics has increased drastically to battle bacterial infections, including tons of antibiotics are distributed in the biosphere. Due to the indiscriminate use of antibiotics, multiple antibiotic-resistant strains have emerged, as the antibiotic resistance genes are being transferred to bacteria of terrestrial animals, humans, and pathogens. The increased public awareness of the negative drawbacks caused by over-exposure to antibiotics, also the emergence of multiple antibiotic resistant pathogenic stains led to the search for alternatives and unique solutions. One such unconventional, promising method is the interruption of bacterial cell to cell communication, which is currently termed QS inhibition. Now-a-days, QS inhibition is the potential objective for antimicrobial chemotherapy. This review summarizes the regulatory factors that attenuate the QS activities of deadly pathogens and discusses their distinctive characteristics. Improving awareness of the natural roles of regulatory elements might be useful in unveiling inhibitor applications to understand how QS is inhibited in pathogenic bacteria by different QS inhibitors.

Advances in the study of exosomes in glaucoma diagnosis and treatment / 中华实验眼科杂志

Exosomes are small vesicles with nanoscale lipid bilayer structures, which are secreted by various cells and are widely present in biological fluids, with complex contents and multiple biological functions.Exosomes play an important role in the development of glaucoma.Exosomes in the eye are involved in trabecular meshwork cell regulation by transporting glaucoma-associated proteins, regulating the Wnt signaling pathway, and affecting extracellular matrix turnover, thereby affecting the atrial circulation.Microglial exosomes mediate retinal neuroinflammation and related inflammatory signaling pathways.In addition, the stable presence of exosomes in intraocular fluid, in which differentially expressed proteins, RNA and other contents give exosomes potential as glaucoma biomarkers.In the treatment of glaucoma, stem cell-derived exosomes inhibit glial cell activation and neuroinflammation, reduce the loss of retinal ganglion cells, and act as neuroprotective agents.Exosomes can cross the blood-retinal barrier, deliver neurotrophic factors, drugs or other therapeutic molecules to target cells, regulate the function of target cells, and provide a new therapeutic tool for glaucomatous optic nerve degeneration.This paper summarized the research progress in the field of glaucoma and exosomes at home and abroad, and reviewed the role of exosomes and related mechanisms in the development, diagnosis, and treatment of glaucoma, expecting to provide new ideas for the early diagnosis and treatment of glaucoma.

New avenues for systematically inferring cell-cell communication: through single-cell transcriptomics data

For multicellular organisms, cell-cell communication is essential to numerous biological processes. Drawing upon the latest development of single-cell RNA-sequencing (scRNA-seq), high-resolution transcriptomic data have deepened our understanding of cellular phenotype heterogeneity and composition of complex tissues, which enables systematic cell-cell communication studies at a single-cell level. We first summarize a common workflow of cell-cell communication study using scRNA-seq data, which often includes data preparation, construction of communication networks, and result validation. Two common strategies taken to uncover cell-cell communications are reviewed, e.g., physically vicinal structure-based and ligand-receptor interaction-based one. To conclude, challenges and current applications of cell-cell communication studies at a single-cell resolution are discussed in details and future perspectives are proposed.

The liver injury following ischemia and reperfusion is worse in experimental knockout heterozygote mouse model for expression of connexin 43

Abstract Purpose: To evaluate that Connexin (Cx43) plays a role in lesions after hepatic ischemia/reperfusion (IR) injury. Methods: We use Cx43 deficient model (heterozygotes mice) and compared to a wild group. The groups underwent 1 hour ischemia and 24 hours reperfusion. The heterozygote genotype was confirmed by PCR. We analyzed the hepatic enzymes (AST, ALT, GGT) and histology. Results: The mice with Cx43 deficiency showed an ALT mean value of 4166 vs. 307 in the control group (p<0.001); AST mean value of 7231 vs. 471 in the control group (p<0.001); GGT mean value of 9.4 vs. 1.7 in the control group (p=0.001); histology showed necrosis and inflammation in the knockout group. Conclusions: This research demonstrated that the deficiency of Cx43 worses the prognosis for liver injury. The topic is a promising target for therapeutics advancements in liver diseases and procedures.

Role of neuron and non-neuronal cell communication in persistent orofacial pain

It is well known that trigeminal nerve injury causes hyperexcitability in trigeminal ganglion neurons, which become sensitized. Long after trigeminal nerve damage, trigeminal spinal subnucleus caudalis and upper cervical spinal cord (C1/C2) nociceptive neurons become hyperactive and are sensitized, resulting in persistent orofacial pain. Communication between neurons and non-neuronal cells is believed to be involved in these mechanisms. In this article, the authors highlight several lines of evidence that neuron-glial cell and neuron macrophage communication have essential roles in persistent orofacial pain mechanisms associated with trigeminal nerve injury and/or orofacial inflammation.

Bone marrow mesenchymal stem cells interactions with hepatocytes and hepatic stellate cells on different stiff substrates / 中华肝脏病杂志

Objective@#To explore the effect of substrate mechanical microenvironment and cell-cell interaction on differentiation of bone marrow mesenchymal stem cells (BMSCs), intrahepatic cellular function and phenotype.@*Methods@#Bone marrow mesenchymal stem cells (BMSCs)-hepatocytes (HCs) and BMSCs-hepatic stellate cells (HSCs) were co-cultured on polyvinyl alcohol (PVA) hydrogel substrates at different stiffness (4.50 ± 0.47 kPa, 19.00 ± 3.51 kPa and 37.00 ± 2.09 kPa) by non-contact co-culture method. Furthermore, the effect of substrate mechanical microenvironment on BMSCs, HCs and HSCs and the activation and proliferation of HCs under different co-cultured condition was studied. A Student's t-test was used to compare the two groups.@*Results@#The expression ofα-smooth muscle actin (α-SMA) and collagenα1- I (Col1A1) in BMSCs and HSCs cultured on its own increased with increase of substrate stiffness. After 72 h, the expression of albumin (ALB) of HCs on three stiff substrates was significantly higher than that of 24 and 48 h. Moreover, the expression of ALB of HCs increased with the increase of substrate stiffness. During the co-culture of BMSCs and HSCs, BMSCs of all three stiffness substrates promoted the expression ofα-SMA, Col1A1 in HSCs, but reduced the expression of PPARγin HSCs cells, thererby promoted the activation of HSCs, with apparent stiffness at 37 kPa. HSCs promoted the expression of ABL in BMSCs at three stiff substrates, but inhibited the expression of alpha-SMA and Col1A1 in BMSCs at 37 kPa, suggesting that co-culture had inhibited the differentiation of BMSCs myofibroblasts, and promoted the differentiation of hepatocyte-like cells, especially at high stiff substrates. In the co-culture of BMSCs and hepatic parenchymal cells, BMSCs had promoted the proliferation of hepatic parenchymal cells at 4.5 kPa. Further, hepatic parenchymal cells had inhibited the expression ofα-SMA in BMSCs, and promoted the expression of Alb, with inhibition of BMSCs differentiation towards myofibroblasts.@*Conclusion@#The differentiation of BMSCs affects the substrate mechanical microenvironment, co-culture of HCs and HSCs. Simultaneously, affecting the function of hepatocytes in relation to the mechanical state of the substrates.

Super “STAR” in translational medicine: Current status and prospects of exosome-related diagnosis and treatment technologies / 第二军医大学学报

Recently, exosome has gained great attention in the field of biomedical research, especially in precision medicine-related diagnostic technology and clinical transformation of therapeutic strategies. There have been a large number of exosome-related studies involving non-invasive diagnosis of diseases, liquid biopsy of tumor, development of precision drugs and observation of clinical efficacy. Exosomes possess four biological characteristics: stable, trackable, active and real-time, which make them the key factors for the next generation “STAR” of translational medicine. Since 2014 exosomerelated studies began to show an explosive increase, and several exosome-associated patent technologies or products have appeared. This article summarizes the research history, biological characteristics and clinical exploration of exosomes, and analyzes the prospects of exosome-related technology.

Research progress on role of exosomes-shuttle-RNAs within central nervous system / 中国药理学通报

Exosomes are nanoscale vesicles produced and secre-ted into extracellular fluid by all cells. They mediate cell com-munication through carrying and transferring informational car-goes ( proteins, nucleic acids, lipids and so on ) to recipient cells. In central nervous system, exosomes can be released from all cell types including neurons, neural stem cells and neuroglia cells. These exosomes shuttle nucleic acids ( miRNAs, mRNAs and so on) and play an important role in nervous system devel-opment and function as well as diseases including Alzheimer's disease and drug addiction. Furthermore, the functional effects and targeting characteristics of exosomes-shuttle-RNAs suggest that exosomes-shuttle-RNAs can be diagnostic and therapeutic targets. In this review, we elaborate the effects, functions and mechanisms of exosomes-shuttle-RNAs in order to gain a new recognition of CNS development and diseases.

Connexin 43 and tumors / 国际肿瘤学杂志

Cell gap junction is a special protein channel.Gap junction-mediated exchange of information between cells is crucial for cell growth,differentiation and tissue homeostasis.Connexin 43 (Cx43) is one of the members of the gap junction protein family.In recent years,researches show that abnormal Cx43 gene expression leads to the cell gap junctional communication dysfunction,which is closely related to the occurrence,metastasis and prognosis of a variety of tumors.Cx43 is expected to become a new target for clinical diagnosis and treatment of tumors.

In vitro study on interaction between esophageal stromal fibroblasts and esophageal carcinoma cells / 重庆医学

Objective To conduct the in vitro study on the changes of gene and biological characteristics of different esophageal interstitial fibroblasts after their indirect contact wish esophageal cancer cell lines.Methods The mRNA levels of Vimentin,α-SMA,TGF-β1,HGF,MMP2 and MMP9 in normal esophageal interstitial fibroblasts(NFs),atypical hyperplasia interstitial fibroblasts(AFs) and cancer related fibroblasts(CAFs) and PCNA mRNA in esophageal carcinoma cell line were detected after their indirectly mutual contact.The invasion test of carcinoma cell line was conducted.Results From NFs,AFs to CAFs,the expression of Vimentin mRNA had no difference.The mRNA expressions of α-SMA,TGF-β1,HGF,MMP2 and MMP9 were gradually increased.After indirectly mutual contact with esophageal carcinoma cell line,the mRNA expressions of α-SMA,TGF-β1,HGF,MMP2 and MMP9 in NFs and AFs were up-regulated,and the difference was statistically significant(P＜0.05),while the related mRNA expression in CAFs had no obvious change.The expression of PCNA mRNA in esophageal carcinoma cell line had no change after contact with NFs,but the expression of PCNA mRNA was significantly up-regulated after interaction with AFs contacting with CAFs.Conclusion The esophageal carcinoma cells and esophageal interstitial fibroblasts could affect the proliferation activity and invasive characteristics of counterparts.

Effects of cell-to-cell communication and histone acetyltransferase on the change of osteogenic differentiation ability among single-cell clones from healthy periodontium with heterogeneity of osteogenic differentiation abilities / 中华口腔医学杂志

Objective@#To investigate the effect of cell-to-cell communication amongst single-cell clones from healthy periodontium with different osteogenic differentiation potentials on change of osteogenic differentiation capabilities and the role histone acetyltransferase partaken in this process.@*Methods@#In order to research the change of osteogenic differentiation ability via cell-to-cell communication, indirect co-culture method was used by placing two single-cell clones with different osteogenesis potentials in each of the 6-well plates. Blank control, weak and strong osteogenic groups were set up, corresponding to Transwell chambers with blank, cells of weak osteogenesis ability and cells of strong osteogenesis ability, respectively. Each group was made in triplicate. After co-culture for four days, Transwell chamber was removed. Quantitative real-time PCR (qPCR) and alizarin red staining were employed to detect the change of osteogenic differentiation ability. The acetylation level of H3 was measured by using Western blotting. Histone acetyltransferases were detected by qPCR.@*Results@#Single-cell clones were ensured from mesenchymal stem cells by flow cytometer, the positive expression of CD29, CD90, CD105, CD146 was (99.80±0.02)%, (99.36±0.18)%, (99.41±0.05)% and (95.10±2.11)%, respectively. And CD31 and CD34 expression were (0.29±0.11)% and (0.22±0.13)%, respectively. Alizarin red and oil red O staining confirmed that single-cell clones had the abilities of adipogenesis and osteogenesis. Alkaline phosphatase (ALP) and alizarin red staining indicated that different single-cell clones were heterogeneity in osteogenesis differentiation. Indirect co-culture indicated that the mRNA expression of osteocalcin (OCN) were 14.24±5.60 and 4.78±2.90, respectively and Runt-related transcription factor 2 (RUNX2) were 2.75±1.44 and 1.61±0.44, respectively, in strong and weak osteogenic groups. They were significantly higher compared to the blank group (the mRNA expression of OCN and RUNX2 were 1.00±0.47 and 1.00±0.39, respectively). The expression of OCN and RUNX2 were also higher in strong osteogenic group than that in weak osteogenic group (P<0.05). The mean gray level of the acetylation of H3 in strong osteogenic group (0.76±0.09) and weak osteogenic group (0.54±0.12) were also higher than that in the blank group (0.30±0.04)(P<0.05). qPCR results showed that KAT6A in strong osteogenic group exhibiting higher expression (P<0.05) compared to weak osteogenic group and the blank group, which were corresponding to the changes of acetylation levels.@*Conclusions@#Single-cell clones from healthy periodontium showed heterogeneity in osteogenic differentiation abilities. Single-cell clones with strong osteogenesis abilities had an advantage over others by promoting others' osteogenesis differentiation and this change mediated by cell-to-cell communication might be caused by modulating KAT6A to affect the acetylation level of histone.

Development of exosomes biogenesis and secretion mechanisms / 解放军医学杂志

Exosomes are nano-sized membrane vesicles (30-100nm in diameter) actively secreted by many cell types and generally exist in many body fluids that contain a variety of cargos,such as protein,lipid and nucleic acid.Exosomes play an important role in cross-communication between different cells and closely associate with the development,treatment and prognostic of many diseases.Recently,exosomes have becoming a hot spot in medical research.An overview of current understanding in biogenesis and secretion mechanism,as well as the regulation of exosomes has been laid in present paper.

Party for killing: the social behaviors in Cryptococcus neoformans / 生物工程学报

Fungal pathogens represent an important group of human pathogenic microbes that lead to an unacceptably severe global burden especially due to exceptionally high mortality. For many fungal pathogens, they are widespread saprophytes and human host is not the exclusive niche for their proliferation. Their exceptional capability to survive and thrive within infected host likely stems from their sophisticated strategies in adaptation to diverse biotic and abiotic stressors from natural niches or predators. Among these 'environmental pathogens', Cryptococcus neoformans as a model organism claims the lives of more than half a million annually. Some recent studies indicate that cryptococcal survival both inside and outside of hosts can be coordinated by a combination of social behaviors. In this review, we describe and discuss the social behaviors employed by C. neoformans and address their significant impact on biofilm formation, sexual reproduction and pathogenicity.

A spatial model showing differences between juxtacrine and paracrine mutual oocyte-granulosa cells interactions.

The bidirectional communication between oocytes and granulosa cells are mediated by several factors via a local feedback loop(s). The current model was carried out to study the spatial mutual interaction of porcine denuded oocytes and granulosa cells either in direct contact (juxtacrine) or paracrine co-culture using transwell system. Transwell 0.4 µm polyester membrane inserts were used to permit oocytes-granulosa cells paracrine communication with a distance of 2 mm between them in co-culture. Oocytes were cultured with granulosa cells in a defined basic maturation medium for 44 h. In results, oocyte secreted factors (OSFs; GDF9 and BMP15) temporal expression showed progressive decrement by the end of culture in case of direct contact with granulosa cells while it was increased progressively in the paracrine co-culture groups. However, oocytes that were cultured in direct contact showed a significant increase in blastocyst development after parthenogenetic activation than the paracrine co-cultured ones (20% vs. 11.5%, respectively). By the end of culture, granulosa cell count in direct contact showed a significant decrease than the indirect co-culture group (1.2 × 105 cell/mL vs. 2.1 × 105 cell/mL, respectively). Steroids (P4 and E2) and steriodogenesis enzymes mRNA levels showed significant temporal alterations either after 22 h and 44 h of IVM in both juxtacrine and paracrine co-culture systems (P ≤ 0.05). CX43 was much more highly expressed in the granulosa of the direct contact group than the indirect co-culture group. These results indicate the difference in mutual communication between oocytes and granulosa cells that were cocultured either in direct contact (juxtacrine) or with a short distance (paracrine) and propose a new paradigm to study different ovarian follicular cells interaction.

Role of intercellular gap junction in propofol and sevoflurane anesthesia in rats / 中华麻醉学杂志

Objective To evaluate the role of intercellular gap junction in the propofol and sevoflurane anesthesia in rats. Methods Eighty male Wistar rats weighing 210-260 g were randomly divided into 8 groups (n = 10 each): control group (group C), carbenoxolone group (group CA), propofol group (group P), different doses of carbenoxolone + propofol groups (groups CA1 + P, CA2 + P, CA3 + P), sevoflurane group (group S) and carbenoxolone + sevoflurane group (group CA + S). The animals ware anesthetized with intraperitoneal 10% chloraldurate 4 mg/kg and placed in a stereotactic apparatus to locate the lateral ventricle. In group C, after normal saline (NS) 2 μl was injected into the latersl ventricle, intraperitoneal NS 2 ml was injected. In group CA, after carbenoxolone 200 μg was injected into the lateral ventricle, intraperitoneal NS 2 ml was injected. In groups P,CA1 + P, CA2 + P and CA3 + P, NS 2 μl, and carbenoxolone 200, 300 and 400 μg were injected into the lateral ventricle respectively and then propofol 5 mg/100 g was injected intraperitoneally. Group S inhaled 1% sevoflurane (in increments of 0. 1% ) until the righting reflex was lost. Group CA + S inhaled 1% sevoflurane (in increments of 0.1% ) until the righting reflex was lost after carbenoxolono 200 μg was injected into the lateral ventricle. The time of loss of righting reflex, duration of loss of righting reflex and the sevoflurane concentration when the righting reflex disappeared were recorded. Results The loss of righting reflex did not appear in groups C and CA. Compared with group P, the time of loss of righting reflex was significantly shortened and duration of loss of righting reflex prolonged in groups CA1 + P, CA2 + P, CA3 + P ( P ＜ 0.01 ). The time of loss of righting reflex was significandy shorter in groups CA2 + P, CA3 + P than in group CA1 + P (P ＜ 0.05). The sevoflurane concentration when the righting reflex disappeared was significantly lower in group CA + S than in group S ( P ＜ 0.05 ). There was no significant difference in the time of loss of righting reflex and duration of loss of righting reflex between CA + S and S groups ( P ＞ 0.05). Conclusion Although inhibition of the function of gap junction can strengthen the anesthetic effects of propofol and sevoflurane, it is not the major mechanism.

Aberrant gap junction and tumor / 国际肿瘤学杂志

Gap junctions are membrane structures made of intercellular channels that allow directly exchange of material and information between adjacent cells. It is the structural basis of gap junctional intercellular communication. Gap junction is aberrant frequently in variety of cancers, which relatives with tumor genesis and metastasis. New anti-cancer drugs targeting gap junctions will be a new direction for tumor treatment.

Functions of intracytoplasmic connexin in tumor progression / 肿瘤研究与临床

A considerable amount of evidence established that gap junctional intercellular communication (GJIC) suppresses tumor development by halting the stage of tumor promotion.Consistently,GJIC is downregulated in tumors.The downregulation of GJIC is caused by not only the reduced expression level of connexin proteins but also their aberrant cytoplasmic localization.Although it has been thought long that cytoplasmic localization of conncxin proteins is merely one of the mechanisms of the downregu]ation of GJIC,careful studies with human tumor samples indicated that the expression level of intracytoplasmic connexin proteins had different biological functions.

Interaction between hepatic stellate cells and hepatocellular carcinoma / 国际肿瘤学杂志

Hepatic stellate cells(HSCs)are key sources of extraeellular matrix during liver fibrosis and in normal liver.During chronic injury,HSCs transform into myofibroblast-like cells,causing liver fibrosis.Hepatocellular carcinoma iS multiple factors disease.There are considerable HSCs infihration in the extracellular matrix of hepatocellular carcinoma.Investigation the interaction between HSCs and hepatocellular carcinoma Can provide a new thinking of hepatocellular carcinoma therapy.

Extracellular Toxicity of Motor Neuronal Cells Expressing Mutant Cu/Zn Superoxide Dismutase in Familial ALS Cell Line Model

BACKGROUND: The objective of this study is to identify the extracellular toxicity of motor neuronal cells expressing mutant copper-zinc superoxide dismutase in the model of familial amyotrophic lateral sclerosis (FALS), and to investi-gate their possible mechanisms in motor neuron death. METHODS: We have set up a model for FALS by transfecting the motor neuron cell line VSC4.1 with plasmids directing the constitutive expression of either wild-type human Cu/Zn superoxide dismutase or a mutant of this enzyme, G93A. The co-culture model of motor neuronal cells expressing both mutant and wild-type Cu/Zn superoxide dismutases were used. Cell toxicity was induced by aphidocholin and viability was determined by a MTT assay. The observed values were compared with predictive values in G93A+VSC4.1 as well as WT+VSC4.1 co-culture groups. RESULTS: In the co-culture group with G93A and VSC4.1, the observed cell viability was significantly lower than what was predicted, suggesting that the G93A affected the viability of VSC4.1. However, in the co-culture group with WT and VSC4.1, WT did not decrease the viability of VSC4.1. CONCLUSIONS: The G93A cells have extracellular toxicity, which could be a result of some kind of cell-to-cell communications between motor neuronal cells.