Motility Ability Research Articles

Potential Role of the Circadian Clock in the Regulation of Cancer Stem Cells and Cancer Therapy.

Circadian rhythms, including sleep/wake cycles as well as hormonal, immune, metabolic, and cell proliferation rhythms, are fundamental biological processes driven by a cellular time-keeping system called the circadian clock. Disruptions in these rhythms due to genetic alterations or irregular lifestyles cause fundamental changes in physiology, from metabolism to cellular proliferation and differentiation, resulting in pathological consequences including cancer. Cancer cells are not uniform and static but exist as different subtypes with phenotypic and functional differences in the tumor microenvironment. At the top of the heterogeneous tumor cell hierarchy, cancer stem cells (CSCs), a self-renewing and multi-potent cancer cell type, are most responsible for tumor recurrence and metastasis, chemoresistance, and mortality. Phenotypically, CSCs are associated with the epithelial-mesenchymal transition (EMT), which confers cancer cells with increased motility and invasion ability that is characteristic of malignant and drug-resistant stem cells. Recently, emerging studies of different cancer types, such as glioblastoma, leukemia, prostate cancer, and breast cancer, suggest that the circadian clock plays an important role in the maintenance of CSC/EMT characteristics. In this review, we describe recent discoveries regarding how tumor intrinsic and extrinsic circadian clock-regulating factors affect CSC evolution, highlighting the possibility of developing novel chronotherapeutic strategies that could be used against CSCs to fight cancer.

MACC1-Dependent Antitumor Effect of Curcumin in Colorectal Cancer.

Metastasis is the main reason for the high mortality rate of colorectal cancer (CRC) patients. Despite the whole improvement in the field of cancer medicine, the treatment options for the patient in the late stages are very restricted. Our previous studies have elucidated metastasis-associated in colon cancer 1 (MACC1) as a direct link to metastasis formation. Therefore, we have aimed to inhibit its expression by using natural products, which are recently the center of most studies due to their low side effects and good tolerability. In this study, we have investigated the effect of one of the promising natural products, curcumin, on MACC1 expression and MACC1-induced tumor-promoting pathways. Curcumin reduced the MACC1 expression, restricted the MACC1-induced proliferation, and was able to reduce the MACC1-induced cell motility as one of the crucial steps for the distant dissemination of the tumor. We further showed the MACC1-dependent effect of curcumin on clonogenicity and wound healing. This study is, to our knowledge, the first identification of the effect of curcumin on the restriction of cancer motility, proliferation, and colony-forming ability by using MACC1 as a target.

The in Vitro Fermentation of Cordyceps militaris Polysaccharides Changed the Simulated Gut Condition and Influenced Gut Bacterial Motility and Translocation.

The motility ability of intestinal lipopolysaccharide (LPS)-producing bacteria determines their translocation to the enterohepatic circulation and works as an infectious complication. In this study, the health effects of Cordyceps militaris polysaccharides (CMPs) were re-evaluated based on whether these polysaccharides could affect the motility of gut commensal LPS-producing bacteria and impede their translocation. The results showed that CMP-m fermentation in the gut could change the chemical environment, leading to a decrease in velocity and a shift in the motility pattern. Further study suggested that detachment/fragmentation of flagella, decreased motor forces, and changed chemical conditions might account for this weakened motility. The adhesion and invasion abilities of gut bacteria were also reduced, with lower expression of virulence-related genes. These results indicated that the health regulation effects of CMP-m might be through decreasing the motility of LPS-producing bacteria, hindering their translocation and therefore reducing the LPS level in the enterohepatic circulation.

In vitro effects of the green synthesized silver and nickel oxide nanoparticles on the motility and egg hatching ability of Marshallagia marshalli

BackgroundGastrointestinal nematodes are one of the serious health problems on the human society and in the livestock industry. Marshallagia marshalli is one of the most prevalent gastrointestinal nematodes in small ruminant, have subtle but more significant adverse effects on the health and fitness of their hosts.AimIn this study, green synthesized nickel oxide (NiO) and silver (Ag) nanoparticles (NPs) have been checked to evaluate the possible antiparasitic effects of nickel oxide and silver nanoparticles on Marshallagia marshalli.MethodsThe characterization of synthesized NiO NPs and Ag NPs was confirmed using the scanning electron microscopy (SEM), X-Ray diffraction (XRD), and UV–Visible spectroscopy. The adult worms were incubated with various concentrations of NiO and Ag NPs with the quantity of; 1, 2, 4, 8, 12, and 16 ppm for 24 h. Mobility and egg hatching abilities of the parasites were recorded at 4-h intervals.ResultsThe results showed that both of the nanoparticles NiO and Ag NPs have anthelmintic activity against Marshallagia marshalli. The anthelmintic effects increased with an increase in the concentration of nanoparticles and the incubation time.ConclusionThe outcome data concluded that Ag-NPs possess a higher level of efficacy than NiO NPs.

Association of Biofilm Inducer with bla VIM, bla IMP, and bla NDM in Pseudomonas aeruginosa Isolates.

Pseudomonas aeruginosa (P. aeruginosa) is a ubiquitous opportunistic organism that is hard to treat. This study aimed to investigate the association of bla VIM, bla IMP, and bla NDM prevalence with Cyclic di-GMP (c-di-GMP) in P. aeruginosa. To this end, 27 clinical isolates of P. aeruginosa were obtained from different hospitals in Baghdad, Iraq. The phenotypic detection of carbapenem and biofilm assays was performed by the M63 minimal medium, supplemented with glucose, magnesium sulfate. The polymerase chain reaction was utilized to detect carbapenem genes. The results showed that the isolates were highly resistant to Imipenem (37%) and Meropenem (63%). Imipenem (37%) and Meropenem (63%) demonstrated a moderate sensitivity against P. aeruginosa. The P. aeruginosa No.5 showed high resistance to carbapenem by bla VIM +, bla IMP +, and bla NDM +, followed by a robust biofilm confirmed with c-di-GMP levels and the twitching motility ability. Upon these findings, the use of antibiotics should be restricted to severe bacterial infections to avoid the rapid emergence of new resistant isolates, which leads to the hard treatment of infection with P. aeruginosa. It is highly recommended that these findings be notified for infectious control. Future studies can investigate the link between transferable resistant genes and c-di-GMP values.

Fucoxanthin prevents breast cancer metastasis by interrupting circulating tumor cells adhesion and transendothelial migration.

Metastasis is the leading cause of cancer-related death and a critical challenge in improving cancer treatment today. Circulating tumor cells (CTCs) adhesion to and across the vascular endothelium are critical steps in the establishment of micrometastatic foci away from the primary tumor. Therefore, we believe that interrupting CTCs adhesion to endothelium and transendothelial migration may efficiently prevent cancer metastasis. Fucoxanthin (Fx) is an algal carotenoid widely distributed in brown algae, macroalgae, and diatoms. Previous studies have found that Fx has various pharmacological activities, including antidiabetic, antioxidant, anti-inflammatory, anti-obesity, antimalarial, anticancer, and so on. However, it remains unclear whether Fx has a preventive effect on cancer metastasis. Here, we found that Fx interrupts breast cancer cells MCF-7 adhesion to endothelium and transendothelial migration, thus inhibiting CTCs-based pulmonary metastasis in vivo. The hetero-adhesion assay showed that Fx significantly inhibited the expression of inflammatory factor-induced cell adhesion molecules (CAMs) and the resulting adhesion between MCF-7 cells and endothelial cells. The wound-healing and transwell assays showed that Fx significantly inhibited the motility, invasion, and transendothelial migration abilities of MCF-7 cells. However, the same concentration of Fx did not significantly alter the cell viability, cell cycle, apoptosis, and ROS of breast cancer cells, thus excluding the possibility that Fx inhibits MCF-7 cell adhesion and transendothelial migration through cytotoxicity. Mechanistically, Fx inhibits the expression of CAMs on endothelial cells by inhibiting the NF-кB signaling pathway by down-regulating the phosphorylation level of IKK-α/β, IкB-α, and NF-кB p65. Fx inhibits transendothelial migration of MCF-7 cells by inhibiting Epithelial-to-mesenchymal transition (EMT), PI3K/AKT, and FAK/Paxillin signaling pathways. Moreover, we demonstrated that Fx significantly inhibits the formation of lung micrometastatic foci in immunocompetent syngeneic mouse breast cancer metastasis models. We also showed that Fx enhances antitumor immune responses by substantially increasing the subsets of cytotoxic T lymphocytes in the peripheral immune system. This new finding provides a basis for the application of Fx in cancer metastatic chemoprevention and suggests that interruption of the CTCs adhesion to endothelium and transendothelial migration may serve as a new avenue for cancer metastatic chemoprevention.

Into the understanding the multicellular lifestyle of Proteus mirabilis on solid surfaces.

Indwelling urinary catheterization can lead to the development of catheter-associated urinary tract infections (CAUTIs), an important type of nosocomial infection, as well as other medical issues among institutionalized adults. Recently, Proteus mirabilis was highlighted as the important cause of CAUTIs. The pathogenicity of P. mirabilis is dependent on two multicellular types of surface colonization: the adherence and swarming motility. Adhesion, mostly mediated by fimbrial and nonfimbrial adhesins, is important for the initiation of biofilm formation. Moreover, the production of urease frequently results in biofilm crystallization, which leads to the blockage of catheters. The heterologous polymeric matrix of the biofilm offers protection against antibiotics and the host immune system. P. mirabilis displays remarkable motility abilities. After contact with solid surfaces, hyper-flagellated cells are able to rapidly migrate. The importance of swarming motility in CAUTIs development remains controversial; however, it was indicated that swarming cells were able to co-express other virulence factors. Furthermore, flagella are strong immunomodulating proteins. On the other hand, both biofilm formation and swarming motility implicates multiple inter- and intraspecies interactions, which might contribute to the pathogenicity.

TGF-β generates a population of cancer cells residing in G1 phase with high motility and metastatic potential via KRTAP2-3.

Transforming growth factor β (TGF-β) increases epithelial cancer cell migration and metastasis by inducing epithelial-mesenchymal transition (EMT). TGF-β also inhibits cell proliferation by inducing G1 phase cell-cycle arrest. However, the correlation between these tumor-promoting and -suppressing effects remains unclear. Here, we show that TGF-β confers higher motility and metastatic ability to oral cancer cells in G1 phase. Mechanistically, keratin-associated protein 2-3 (KRTAP2-3) is a regulator of these dual effects of TGF-β, and its expression is correlated with tumor progression in patients with head and neck cancer and migratory and metastatic potentials of oral cancer cells. Furthermore, single-cell RNA sequencing reveals that TGF-β generates two populations of mesenchymal cancer cells with differential cell-cycle status through two distinctive EMT pathways mediated by Slug/HMGA2 and KRTAP2-3. Thus, TGF-β-induced KRTAP2-3 orchestrates cancer cell proliferation and migration by inducing EMT, suggesting motile cancer cells arrested in G1 phase as a target to suppress metastasis.

Carbon dioxide can inhibit biofilms formation and cellular properties of Shewanella putrefaciens at both 30 °C and 4 °C

Shewanella putrefaciens (S. putrefaciens), which is a common specific spoilage organism (SSO) of marine fish, has strong spoilage ability even under low-temperature conditions. Carbon dioxide (CO2) was widely applied to control microorganisms in aquatic products package. To explore the regulation mechanism of CO2 on biofilm formation and cell properties of S. putrefaciens, the dynamic formation process of biofilms, cellular surface properties, and cellular metabolic characteristics of S. putrefaciens at both 30 °C and 4 °C in pure CO2 gas were evaluated. As evidenced by the crystal violet staining method, confocal laser scanning microscopy (CLSM) analysis, and field emission scanning electron microscopy (FESEM) observation, dynamic formation process of S. putrefaciens biofilms was apparently delayed by CO2 with integral cellular morphology. The number and viability of sessile cells in S. putrefaciens biofilms was significantly lower than those in normal air composition. The changes in cellular surface properties, such as decreased auto-aggregation and hydrophobicity, might be one of the reasons why biofilms were inhibited by CO2. Inhibition of swimming and swarming motility ability by CO2 could also be observed with significantly shorter bacterial halo diameter. What’s more, cellular metabolism was significantly decreased by CO2 according to the results of ATP content, ATPase activity and extracellular proteolytic activity. The influence of CO2 could be both observed whether combined with 30 °C or 4 °C. However, the inhibition produced by CO2 was more pronounced at the incubation temperature of 4 °C. In summary, it could be concluded that the dynamic formation process of S. putrefaciens biofilms and cellular metabolic properties could be inhibited by CO2. This research provided a theoretical basis for better application of CO2 to regulate spoilage microorganisms.

FliA, flrB, and fliR regulate adhesion by controlling the expression of critical virulence genes in Vibrio harveyi

Bacteria adhesion to fish mucus is a crucial virulence mechanism. As the initial step of bacterial infection, adhesion is impacted by bacterial motility and environmental conditions. However, its molecular mechanism is yet unclear. In this study, a significant decrease in gene expression of adhesion-deficient Vibrio harveyi was observed when the bacteria were subjected by Cu2+(50 mg/L), Pb2+(100 mg/L), Hg2+(25 mg/L), and Zn2+(50 mg/L). The genes fliA, fliR, and flrB were responsible for flagellation; being crucial for adhesion, these genes were identified and silenced via RNAi. After silencing of these genes by RNAi technology, the ability of adhesion, biofilm formation, motility, and flagella synthesis of V. harveyi were considerably reduced. Compared with the control group, it was observed that the expression levels of fliS, fliD, flgH, and flrC were significant down-regulated in fliR-RNAi, flrB-RNAi, and fliA-RNAi. This data indicates that the expression levels of most virulence genes are affected by fliA, fliR, and flrB. Also, the expression of fliA, fliR, and flrB can be influenced by the salinity, temperature, and pH. The results show that: (1) fliA, fliR, and flrB have important roles in the adhesion of V. harveyi; (2) fliA, fliR, and flrB can regulate bacterial adhesion by affecting its motility, and biofilm formation; (3) fliA, fliR, and flrB can regulate adhesion ability of V. harveyi in different environments.

P-063 Multivariate analysis identifies oxidative stress levels and acrosome status of motile spermatozoa as independent predictors of motile sperm hyaluronan binding ability

Abstract Study question Is it possible to predict motile sperm hyaluronan binding ability (HBA) from motile sperm functional parameters? Summary answer Using multivariate analysis, oxidative stress levels and acrosome status of motile spermatozoa, derived from semen swim-up, were identified as predictors of sperm HBA. What is known already Semen analysis is a gold standard practice for fertility evaluation. However, motility and morphology of spermatozoa are not always indicative of the molecular makeup of sperm cells. In this context, several sperm functional tests were developed to enhance our understanding of spermatozoa biology. Interestingly, several studies have shown that the plasma membrane of mature sperm cells contain hyaluronan binding sites. HBA was associated with intact acrosome, decreased DNA damage, and high viability. Nevertheless, it has not been demonstrated yet if hyaluronan binding ability can be predicted solely by swim-up derived- motile spermatozoa functional parameters. Study design, size, duration A prospective study was performed at Al-Hadi Medical Center, beirut, Lebanon, between January and July 2020. Freshly ejaculated semen samples obtained from infertile men with concentration of ≥ 20 x 106/ml and with total sperm motility of ≥ 30% were included. The primary outcome was to assess if the motile sperm functional parameters may influence HBA. A sample size of 54 was calculated using power = 85% and alpha = 5% for multiple linear regression. Participants/materials, setting, methods 54 semen samples were assessed according to WHO guidelines (2010). Thereafter, samples were processed using the semen swim-up technique. Supernatants containing motile spermatozoa were collected for further analysis. In motile spermatozoa-enriched fractions, chromatin integrity was assessed using toluidine blue (TB) staining. Oxidative stress levels were detected using a nitroblue tetrazolium (NBT) test. Acrosome status was determined using triple staining technique. HBA was evaluated via a commercially available hyaluronan binding assay (HBA® Assay). Main results and the role of chance In the motile spermatozoa-enriched fractions, mean ± standard deviations for concentration, progressive motility, non-progressive motility and normal morphology were 26.17±11.48, 76±18.97, 20.94±12.61 and 0.75 ± 1.4, respectively. In addition, mean ± standard deviations for TB + cells, NBT + cells, living spermatozoa with intact acrosome, and HBA were 16.42 ± 13.4, 57.4 ± 9.4, 93.9 ±3.2, and 48.98±11.95, respectively. The values of the HBA had a non-normal distribution; therefore, these values were first linearized by taking the logarithm of the outcome. Afterwards, multiple linear regression (MLR) was used to predict the outcome. The overall regression of the final model was statistically significant (R2 = 0.346), F(4.43) =5.962, p = 0.001. The results of the final MLR model indicated that a unit increase in non-progressive motility (%) (p = 0.002) and NBT + cells (%) (p = 0.009) increased the HBA by 1.505 units and 1.409 units, respectively. However, a unit increase in dead spermatozoa with unreacted acrosome (%) (p = 0.032) and living spermatozoa with reacted acrosome (%) (p = 0.026) decreased the HBA by 1.317 units and 1.342 units, respectively. Limitations, reasons for caution This is an interim study and these results should be taken as preliminary. In order to confirm these findings, further studies including larger sample size and motile spermatozoa derived from semen samples with abnormal parameters (such as severe asthenozoospermia, leukocytospermia, severe oligozoospermia) are required. Wider implications of the findings Several studies indicated that using damaged spermatozoa may affect the intracytoplasmic sperm injection (ICSI) outcomes. In addition, using damaged spermatozoa during fertilization may predispose the offspring to various diseases later in life. These results may be considered as an impetus to reconsider sperm selection during ICSI. Trial registration number Not applicable

Biological Relevance of Free Radicals in the Process of Physiological Capacitation and Cryocapacitation

Before fertilization, spermatozoa must undergo a process called capacitation in order to fulfill their fertilization potential. This includes a series of structural, biochemical, and functional changes before a subsequent acrosome reaction and fusion with the oocyte. However, low temperatures during cryopreservation may induce a premature activation of capacitation-like changes, also known as cryocapacitation, immediately after thawing, which may lead to a decreased viability, motility, and fertilization ability of cryopreserved spermatozoa. Furthermore, cryopreservation is responsible for the overgeneration of reactive oxygen species (ROS) such as superoxide, hydrogen peroxide, and hydroxyl radicals, which may result in the development of oxidative stress, cell membrane damage, and lipid peroxidation. Despite that, both capacitation and cryocapacitation are considered to be oxidative events; however, potential beneficial or detrimental effects of ROS depend on a wide array of circumstances. This review summarizes the available information on the role of free radicals in the process of capacitation and cryocapacitation of spermatozoa.

SdiA Enhanced the Drug Resistance of Cronobacter sakazakii and Suppressed Its Motility, Adhesion and Biofilm Formation.

Cronobacter sakazakii is a common foodborne pathogen, and the mortality rate of its infection is as high as 40–80%. SdiA acts as a quorum sensing regulator in many foodborne pathogens, but its role in C. sakazakii remains unclear. Here, we further determined the effect of the sdiA gene in C. sakazakii pathogenicity. The SdiA gene in C. sakazakii was knocked out by gene editing technology, and the biological characteristics of the ΔsdiA mutant of C. sakazakii were studied, followed by transcriptome analysis to elucidate its effects. The results suggested that SdiA gene enhanced the drug resistance of C. sakazakii but diminished its motility, adhesion and biofilm formation ability and had no effect on its growth. Transcriptome analysis showed that the ΔsdiA upregulated the expression levels of D-galactose operon genes (including dgoR, dgoK, dgoA, dgoD and dgoT) and flagella-related genes (FliA and FliC) in C. sakazakii and downregulated the expression levels of related genes in the type VI secretion system (VasK gene was downregulated by 1.53-fold) and ABC transport system (downregulated by 1.5-fold), indicating that SdiA gene was related to the physiological metabolism of C. sakazakii. The results were useful for clarifying the pathogenic mechanism of C. sakazakii and provide a theoretical basis for controlling bacterial infection.

The Transcription Regulator YgeK Affects Biofilm Formation and Environmental Stress Resistance in Avian Pathogenic Escherichia coli.

Simple SummaryAvian pathogenic Escherichia coli (APEC) is the pathogen responsible for colibacillosis in poultry. Transcriptional regulator ygeK has been shown to decrease APEC’s flagellar formation ability, bacterial motility ability, serum sensitivity, and adhesion ability. However, we did not study the effects of ygeK on biofilm formation and environmental stress resistance in APEC. In this study, we investigated ygeK in APEC biofilm formation and bacterial resistance to different environmental stresses. We also analyzed the multi-level regulation of ygeK in APEC and investigated associations between differentially expressed proteins and key ygeK targets. This work provides a basis for further analysis of APEC pathogenesis mechanisms.Avian pathogenic Escherichia coli (APEC) is one of the most common pathogens in poultry and a potential gene source of human extraintestinal pathogenic E. coli (ExPEC), leading to serious economic losses in the poultry industry and public health concerns. Exploring the pathogenic mechanisms underpinning APEC and the identification of new targets for disease prevention and treatment are warranted. YgeK is a transcriptional regulator in APEC and is localized to the type III secretion system 2 of E. coli. In our previous work, the transcription factor ygeK significantly affected APEC flagella formation, bacterial motility, serum sensitivity, adhesion, and virulence. To further explore ygeK functions, we evaluated its influence on APEC biofilm formation and resistance to environmental stress. Our results showed that ygeK inactivation decreased biofilm formation and reduced bacterial resistance to environmental stresses, including acid and oxidative stress. In addition, the multi-level regulation of ygeK in APEC was analyzed using proteomics, and associations between differentially expressed proteins and the key targets of ygeK were investigated. Overall, we identified ygeK’s new function in APEC. These have led us to better understand the transcriptional regulatory ygeK and provide new clues about the pathogenicity of APEC.

Cluster Differences in Antibiotic Resistance, Biofilm Formation, Mobility, and Virulence of Clinical Enterobacter cloacae Complex

Due to the lack of research on the characteristics of different clusters of Enterobacter cloacae complex (ECC), this study aimed to characterize and explore the differences among species of the ECC. An analysis based on hsp60 showed that Enterobacter hormaechei was predominant in ECC. Interestingly, the antibiotic resistance rates of clusters were different, among which E. hormaechei subsp. steigerwaltii (cluster VIII) and Enterobacter cloacae IX (cluster IX) possessed high resistant rates to ciprofloxacin and levofloxacin, but cluster II (Enterobacter kobei) had low resistant rates. Cluster II exhibited a strong biofilm formation ability. Different motility and protease production ability were shown for distinct clusters. A PCR analysis showed that clusters I, III, VI, VIII, and IX carried more virulence genes, while cluster II had fewer. Clusters I, VIII, and IX with high pathogenicity were evaluated using the Galleria mellonella infection model. Thus, the characteristics of resistance, biofilm-forming ability, mobility, and virulence differed among the clusters. The strains were divided into 12 subgroups based on hsp60. The main clusters of ECC clinical strains were I, II, III, VI, VIII, and IX, among which IX, VIII, and I were predominant with high resistance and pathogenicity, and cluster II (E. kobei) was a special taxon with a strong biofilm formation ability under nutrient deficiency, but was associated with low resistance, virulence, and pathogenicity. Hence, clinical classification methods to identify ECC subgroups are an urgent requirement to guide the treatment of clinical infections.

MicroRNA-138 Abates Fibroblast Motility With Effect on Invasion of Adjacent Cancer Cells.

BackgroundRecent studies have shown aberrant expression of micro-RNAs in cancer-associated fibroblasts (CAFs). This study aimed to investigate miR-138 dysregulation in CAFs in oral squamous cell carcinoma (OSCC) and its effects on their phenotype and invasion of adjacent OSCC cells.MethodsExpression of miR-138 was first investigated in OSCC lesions (n = 53) and OSCC-derived CAFs (n = 15). MiR-138 mimics and inhibitors were used to functionally investigate the role of miR-138 on CAF phenotype and the resulting change in their ability to support OSCC invasion.ResultsExpression of miR-138 showed marked heterogeneity in both OSCC tissues and cultured fibroblasts. Ectopic miR-138 expression reduced fibroblasts’ motility and collagen contraction ability and suppressed invasion of suprajacent OSCC cells, while its inhibition resulted in the opposite outcome. Transcript and protein examination after modulation of miR-138 expression showed changes in CAF phenotype-specific molecules, focal adhesion kinase axis, and TGFβ1 signaling pathway.ConclusionsDespite its heterogeneous expression, miR-138 in OSCC-derived CAFs exhibits a tumor-suppressive function.

Using feeding and motility patterns for ivermectin resistance detecting in Haemonchus contortus larvae

Resistance of Haemonchus contortus to ivermectin has become an increasingly serious problem worldwide. Drug-based control and management of this parasite requires reliable methods for testing drug resistance to evaluate and monitor their anthelmintic effects. In this study, the larval migration inhibition test (LMIT) and the larval feeding inhibition test (LFIT) were used to assess and compare seven strains of H. contortus, including one resistant and one susceptible strain from abroad (UKR and ASS, respectively), and five strains native to China (SXS, WMR, WSR1, WSR2, and WSR3). LFIT results showed that fluorescent-labeled Escherichia coli could be clearly observed after ivermectin (IVM) treatment inside UKR, WMR, WSR1, WSR2, and WSR3 larvae, but not inside ASS and SXS strains. Moreover, LMIT results showed that migration of SXS strain did not change significantly after IVM treatment compared with the susceptible ASS strain, whereas migration increased significantly in the UKR, WMR, WSR1, WSR2, and WSR3 strains. Taken together, SXS was found to be an IVM-susceptible strain, whereas WMR, WSR1, WSR2, and WSR3 were IVM-resistant strains. These results demonstrate that assessment of the motility and feeding ability of H. contortus larvae can be effectively used to determine resistance of H. contortus to IVM.

CD73 and PD-L1 as Potential Therapeutic Targets in Gallbladder Cancer.

Gallbladder cancer (GBC) is one of the most common and aggressive biliary tract cancers with a dismal prognosis. Ongoing clinical trials are evaluating a few selected immune checkpoint inhibitors (ICIs) as monotherapy for the treatment of GBC patients. However, only a subset of patients benefits from these treatments. To improve ICI therapy response, molecular mechanisms that confer resistance to immune checkpoint (IC) blockade needs to be explored. Epithelial-to-mesenchymal transition (EMT) program and cancer stem cells (CSCs) have been implicated as key processes that confer ICI treatment resistance. However, in GBC the EMT-CSC-IC axis has not yet been clearly elucidated. This study aims to examine the aberrant expression of ICs associated with CSC and EMT. We successfully enriched CSCs by utilizing a 3-dimensional culture system and established a reversible EMT model with human GBC NOZ cell line. Notably, ICs CD73 and PD-L1 were closely associated with both CSC and EMT phenotypes. Knockdown of CD73 or PD-L1 reduced the proliferative and motile abilities of both adherent monolayers and anchorage-free spheroids. In conclusion, blocking CD73 and PD-L1 offer a promising therapeutic strategy for targeting highly aggressive populations with CSC and EMT phenotype to improve GBC patient prognosis.

RETRACTED ARTICLE: Anti-aging effect of polysaccharides from the peel of Zanthoxylum schinifolium Sieb. et Zucc. on the nematode Caenorhabditis elegans

This article has been retracted from publication in the Taylor & Francis journal, Acta Agriculturae Scandinavica, Section B — Soil & Plant Science. Following publication, concerns were raised by multiple third-parties around the content of the special issue and the decision-making process. Following an investigation by the Taylor & Francis Publishing Ethics & Integrity team in full cooperation with the Editor-in-Chief, it was confirmed that this article included in Special Issue titled “ Envisage Computer Modelling and Statistics for Agriculture”, guest edited by Gunasekaran Manogaran was not peer-reviewed appropriately, in line with the Journal's peer review standards and policy. As the stringency of the peer review process is core to the integrity of the publication process, the Editor and Publisher have decided to retract all of the articles within the above-named Special Issue. The journal has not confirmed if the authors were aware of this compromised peer review process. The journal is committed to correcting the scientific record and will fully cooperate with any institutional investigations into this matter. The authors have been informed of this decision. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines.

Salmonella Typhimurium fepB negatively regulates C. elegans behavioral plasticity

ObjectivesDauer is an alternative developmental stage of Caenorhabditis elegans (C. elegans) that gives survival benefits under unfavorable environmental conditions. Our study aims to decipher C. elegans dauer larvae development upon Salmonella Typhimurium infection and how the bacterial gene regulating the worm's behavioural plasticity for better survival. MethodsAge-synchronized L4 C. elegans worms were infected with Salmonella Typhimurium 14028s (WT-STM) strain and mutant strains to check the dauer larvae development using 1% SDS. Besides, bacterial load in animals’ gut, pharyngeal pumping rate and viability were checked. Worm's immune genes (e.g., ilys-3, lys-7, pmk-1, abf-2, clec-60) and dauer regulatory genes (e.g., daf-7, daf-11, daf-12, daf-16, daf-3) were checked by performing qRT-PCR under infection conditions. ResultsWe found that deletion of the fepB gene in S. Typhimurium strain became less pathogenic with reduced flagellar motility and biofilm-forming ability. Besides, there was decreased bacterial burden in the worm's gut with no damage to their pharynx. The fepB mutant strain was also able to enhance the immune responses for better survival of worms. Infection with mutant strain could activate dauer signaling via the TGF-β pathway leading to a significant increase in dauer formation than WT-STM infection. ConclusionOur study indicated that the bacteria act as a food source for the growth of C. elegans and development and can act as a signal that might be playing an essential role in regulating the host physiology for their survival. Such a study can help us in understanding the complex host-pathogen interaction benefiting pathogen in host dissemination.