Lung adenocarcinoma (LUAD) is a major subtype of non-small-cell lung cancers (NSCLC). LINC00680 has been characterized as a novel oncogenic lncRNA in LUAD, but its regulatory mechanisms remain largely unclear. This study aimed to explore the subcellular localization of LINC00680 in LUAD and its regulation on the transcriptional process. LUAD cell lines (A549, H1650, and H1299) were used for in vitro and in vivo studies. Results showed LINC00680 depletion resulted in G0/G1 phase arrest of LUAD cells and reduced CDK4 and cyclin D1 expression in H1650 and H1299 cells. LINC00680 overexpression promoted A549 cell proliferation and increased CDK4 and cyclin D1 expression. RNA-fluorescence in situ hybridization (FISH) assay showed that LINC00680 has both cytoplasmic and nuclear distribution in LUAD cells. RNA pulldown and western blotting assays confirmed a physical interaction between LINC00680 and GATA6. In LUAD cells, GATA6 overexpression only slightly suppressed SOX12 transcription. ChIP-qPCR and dual-luciferase assay showed that GATA6 only weakly bound to the SOX12 promoter and decreased its activity. However, when LINC00680 was depleted, these transcriptional suppressive effects were significantly enhanced. These findings suggested that LINC00680 forms a complex with GATA6 and weakens its transcriptional suppressive effect on SOX12 expression. In the nude mice model, LINC00680 overexpression partly abrogated the growth-suppressive effects of GATA6 on A549 derived tumors. In summary, this study revealed a novel LINC00680-GATA6-SOX12 axis in promoting LUAD cell cycle progression and proliferation. Future studies should be conducted for a better understanding of the complex networking of LINC00680 in LUAD.

As an immunosuppressive receptor, T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) play a critical part in cellular immune regulation mediated by pathogen infection. Whereas, TIGIT expression on splenic T cells in hosts infected with Toxoplasma gondii cysts has not been studied. In this study, we detected TIGIT expression and the changes of immune function in the spleen by flow cytometry and real-time PCR (RT-PCR). We found that TIGIT expression on splenic T cells increased significantly post infection. At the same time, splenic TIGIT+TCM cells were activated and transformed into TIGIT+TEM cells during the infection, and the cytotoxicity of TIGIT+ T cells was reduced in the later stage of infection. This study shows that chronic T. gondii infection can upregulate TIGIT expression on the surface of T cells and affect immune cell function.

As an apicomplexan pathogen, Toxoplasma gondii still remains a major threat to public health and requires special attention. In fact, positive attempts to identify more effective antigens to provide protection are important to control toxoplasmosis. Latest scientific advances in T. gondii study hint at the probability of the T. gondii bradyzoite-formation deficient 1 (TgBFD1) as an ideal vaccine candidate, since this molecule plays a critical role in regulating the chronic infection of T. gondii. Thus, BALB/c mouse models of acute and chronic T. gondii infections were used to evaluate the TgBFD1 protection efficacy in this study. Before conducting animal trials, antigen analysis of TgBFD1 was performed using DNAstar software and Western blots. The preliminary results suggested that TgBFD1 should be a potent immunogen. Then, this conclusion is confirmed by ELISA assays. After immunization with rTgBFD1, high levels of specific IgG, IgG1, IgG2a, and cytokines (Interferon γ and interleukin 10) were observed, indicating that TgBFD1 could induce strong protective antibody responses. While TgBFD1-specific IgG antibodies were measurable in vaccinated mice, no protection was observed in the acute T. gondii infection (RH strain) assay. However, a noticeable decrease in brain cysts counts of immunized mice compared with negative controls in the latent T. gondii infection (PRU strain) assay was observed. Taken together, these results indicated that rTgBFD1 had the remarkable ability to elicit both humoral and cellular immune responses and could provide partial protective immunity against chronic T. gondii infection.

The liver fluke Fasciola gigantica has a remarkable ability to establish a long-term infection within the hepatobiliary system of the mammalian definitive host. F. gigantica achieves this by producing excretory-secretory molecules, which have immunomodulatory activities. In an effort to elucidate the immunomodulatory functions of F. gigantica thioredoxin peroxidase protein (FgTPx), we expressed recombinant FgTPx (rFgTPx) in Escherichia coli bacteria and examined its effects on several functions of goat peripheral blood mononuclear cells (PBMCs) in vitro. Sequence analysis revealed that FgTPx is related to a thioredoxin-like superfamily. Western blot analysis showed that rFgTPx was recognized by the sera of goats experimentally infected by F. gigantica. The specific binding of rFgTPx protein to the surface of goat PBMCs was demonstrated by immunofluorescence staining. We investigated the influence of serial concentrations of rFgTPx on various functions of goat PBMCs. All concentrations of rFgTPx increased the secretion of interleukin-2 (IL-2), IL-4, IL-10, IL-17, transforming growth factor-beta (TGF-β), and interferon gamma (IFN-γ), but inhibited PBMC proliferation, migration, and monocyte phagocytosis. Goat PBMCs exposed to 20-40 μg/mL of rFgTPx secreted increased levels of nitric oxide (NO), and 10-40 μg/mL of rFgTPx promoted cell apoptosis. These findings indicate that rFgTPx influences various functions of goat PBMCs by interacting with a large number of cellular targets, ultimately to promote the parasite's survival. The roles of rFgTPx and their interacting proteins warrant further investigation.

Thermally enhanced bioremediation is a promising approach to shorten the bioremediation period of tetrachloroethene (PCE) and trichloroethene (TCE). To clarify the influence that temperature has on stepwise PCE dechlorination and associated microorganisms, this study conducted dechlorination experiments using contaminated soil and groundwater under five distinct temperature conditions (i.e., 15, 20, 25, 30, and 35 °C). PCE and TCE were dechlorinated most rapidly at 25-35 °C, whereas the preferable temperatures for the dechlorination of cis-1,2- dichloroethene (cis-1,2-DCE) and vinyl chloride (VC) were 25-30 °C and 25 °C, respectively. Microbial community analysis revealed that Sulfurospirillum and Geobacter may have a dominant contribution to the dechlorination of PCE to cis-1,2-DCE, whereas Dehalococcoides harboring VC reductase genes are likely major contributors to the dechlorination of cis-1,2-DCE and VC. These results suggest that temperature influences various microbial groups, including major dechlorinating microorganisms, resulting in the different extent of PCE dechlorination. In addition, the microbial community structure greatly changed after the onset of the experiment, whereas the temperature influence of 15-30 °C on the microbial community structure was minor; however, the microbial community was significantly impacted at 35 °C. Collectively, these results suggest that thermally enhanced anaerobic dechlorination at 25 °C is useful for successful dechlorination of chlorinated ethenes in a short period.

The α/β-hydrolase domain (ABHD) proteins belonging to α/β-hydrolase (ABH) superfamily are ubiquitously distributed throughout all the organisms, and their functional roles have been implicated in energy metabolism, cell signaling, growth and development. In our preliminary work, we identified a novel ABHD protein derived from Haemonchus contortus excretory-secretory (ES) proteins (HcESPs) that interacted with host T cells. Here, we demonstrated that H. contortus ABHD (HcABHD) protein, expressed in all life-cycle stages of H. contortus, is a mammalian ABHD17 homolog with immunodiagnostic utility and lipase activity. Given its catalytic activities and immunomodulatory potentials, we further investigated the functional diversity of HcABHD as an individual ES protein in parasite-host interactions. HcABHD protein may serve as depalmitoylase or thioesterase to suppress cell viability, inhibit cell proliferation, induce intrinsic and extrinsic T cell apoptosis, and cause cell cycle arrested at G1 phase. Moreover, recombinant HcABHD stimuli exerted critical controls on T cell cytokine production profiles, predominantly by inhibiting the secretions of interleukin (IL)-4, interferon-gamma (IFN-γ) and transforming growth factor-beta (TGF-β) 1, and promoting IL-10 production. As the immunomodulator acting at the parasite-host interface, HcABHD protein may have potential applications for the vaccine development of therapeutic intervention. Together, these findings may help illuminate the molecular and particularly immunomodulatory aspects of ES proteins and contribute to an enhanced understanding of parasite immune evasion in H. contortus-host biology.

Haemonchus contortus has evolved highly integrated and sophisticated mechanisms to promote coexistence with hosts. The excretory-secretory (ES) products generated by this parasite contribute to the regulation of the host immune response to facilitate immune evasion and induce chronicity, but the proteins responsible for this process and the exact cellular mechanisms have yet to be defined. In this study, we identified 114 H. contortus ES proteins (HcESPs) interacting with host T cells and 15 T cell binding receptors via co-immunoprecipitation and shotgun liquid chromatography-tandem mass spectrometry analysis. Based on bioinformatics analysis, we demonstrated that HcESPs could inhibit T cell viability, induce cell apoptosis, suppress T cell proliferation and cause cell cycle arrest. Furthermore, the stimulation of HcESPs exerted critical control effects on T cell cytokine production profiles, predominantly promoting the secretion of interleukin (IL)-10, IL-17A and transforming growth factor-β1 and inhibiting IL-2, IL-4 and interferon-γ production. Collectively, these findings may provide insights into the interaction between ES proteins and key host effector cells, enhancing our understanding of the molecular mechanism underlying parasite immune evasion and providing new clues for novel vaccine development.

Although the understanding of resistance to oxaliplatin (OXA) chemotherapy in colorectal cancer (CRC) has been sought for many years, drug tolerance remains a major challenge for cancer therapy. Revealing the molecular mechanism of OXA resistance could help to explain the poor prognosis of patients.

Trichomonas vaginalis is a widespread and important sexually transmitted pathogen. Adherence to the surface of the host cell is the precondition for the parasitism and pathogenicity of this parasite. Trichomonas vaginalis adhesion protein 33 (TvAP33) plays a key role in the process of adhesion, but how this protein mediates the adhesion and pathogenicity of T. vaginalis to host cells is unclear.

Toxoplasma gondii is an apicomplexan pathogen infecting 2 billion people and numerous livestock, causing a major threat to economies and human health. Passive-active immunoprophylaxis is an efficient approach to provide protection against toxoplasmosis. T. gondii perforin-like protein 2 (TgPLP2) contains a membrane attack complex/perforin (MACPF) domain, making it a potential vaccine candidate. Here, we aimed to assess the protection efficacy of TgPLP2 using Bagg albino/c (BALB/c) mice model. The Escherichia coli system was used to obtain the recombinant TgPLP2 (rTgPLP2). Mice challenged by anti-rTgPLP2 polyclonal antibodies (PcAb) pretreated tachyzoites showed obviously increased survival outcomes. In addition, mice that passively received anti-rTgPLP2 PcAb following a lethal dose of tachyzoites infection had longer survival time compared with phosphate-buffered saline (PBS) controls. Furthermore, we demonstrated that immunization with rTgPLP2 could prolong survival in RH strain infected mice and resulted in the lowest brain cysts size and number of Prugniaud (PRU) genotype II strain infected mice. High levels of Toxoplasma-specific IgG, IgG1, IgG2a, and cytokines (IFN-γ and IL-10) were produced after two immunizations with rTgPLP2. Together these results indicated that TgPLP2 can induce both humoral and cellular immune responses to protect host against infection and thus is a potential candidate for T. gondii vaccines.

Gastrointestinal nematodes could release excretory-secretory (ES) proteins into the host environment to ensure their survival. These ES proteins act as immunomodulators to suppress or subvert the host immune response via the impairment of immune cell functions, especially in chronic infections. In our preliminary study, Haemonchus contortus adhesion-regulating molecule 1 (HcADRM1) was identified from H. contortus ES proteins (HcESPs) that interacted with host T cells via liquid chromatography-tandem mass spectrometry analysis. However, little is known about HcADRM1 as an ES protein which may play a pivotal role at the parasite-host interface.

A previous study identified that isoform 2 (Hcftt-2) of the 14-3-3 protein of Haemonchus contortus (H. contortus) could suppress immune functions of goat peripheral blood mononuclear cells (PBMCs) and might be a potential vaccine target, as neutralization of the protein function may enhance anti-parasite immunity. In this research, the recombinant Hcftt-2 was evaluated for its immunoprotective efficacy against H. contortus infection in goats. Five experimental goats were immunized twice with rHcftt-2 along with Freund's adjuvant. The five immunized goats and five nonimmunized goats (adjuvant only) were challenged with 5000 L3-stage H. contortus larvae after 14 days of second immunization. Five nonimmunized and uninfected goats (adjuvant only) were set as the uninfected group. A significant increase in the serum immunoglobin G(IgG) and serum IgA levels were identified in the rHcftt-2 immunized animals. The mean eggs per gram in feces (EPG) and the worm burdens of rHcftt-2 immunized group were reduced by 26.46% (p < 0.05) and 32.33%, respectively. In brief, immunization of goats with rHcftt-2 induced moderate protection against H. contortus challenge.

Trichomonas vaginalis is a protozoan parasite, widely recognized as the most prevalent non-viral sexually transmitted infection (STI) globally. This infection is linked to various complications, including pelvic inflammatory disease, adverse pregnancy outcomes, and an increased risk of acquiring HIV. Current molecular detection methods for T. vaginalis are often costly and technically challenging.

Ephrin domain containing protein (EPH), a significant excreted and secreted product (ESPs) of Haemonchus contortus, has been identified to have antigenic functions. Over the past years, a new subset of CD4 + T named as T helper 9 cells that secrete interleukin-9 (IL-9) as a signature cytokine is associated with tumor immunity and allergy. Nonetheless, the understanding of immunomodulatory roles of EPH on goat Th9 and other immune cells remains limited. Herein, EPH from H. contortus (HcEPH) was cloned and expressed in pET-28a. Immunofluorescence assay (IFA) was carried-out to localize rHcEPH within H. contortus adult worms and to bind with goat peripheral blood mononuclear cells (PBMCs). Besides, the impact of rHcEPH on signature cytokine IL-9 expression in goat PBMCs was evaluated. Flow cytometry was employed to examine Th9 cells production and cell apoptosis. The results revealed success in the expression and localization of rHcEPH in surface of adult H. contortus gut sections. According to IFA analysis, the rHcEPH protein was capable to react precisely with anti-H. contortus antibodies. Further functional analysis showed that correlation between rHcEPH and host PBMCs significantly enhanced Th9 cell differentiation, IL-9 expression, cell apoptosis efficiency, and cell migration, whereas cell proliferation was suppressed significantly depending on the concentration. Our observations indicated that rHcEPH protein is linked to modulate the host immune cells and could enhance protective immunity by inducing Th9 responses.