Treponema pallidum recombinant protein Tp0768 enhances the ability of HUVECs to promote neutrophil chemotaxis through TLR2/ER stress signaling pathway.

Neutrophils are essential cells involved in inflammation. However, the specific mechanism of neutrophil chemotaxis induced by Treponema Pallidum (T. pallidum) remains unknow. In this study, human umbilical vein endothelial cells (HUVECs) were utilized as target cells to investigate the expression levels of chemokines when stimulated with different concentrations of Tp0768(also known as TpN44.5 or TmpA, a T. pallidum infection dependent antigen). The results indicated that Tp0768 treatment enhanced neutrophil chemotaxis in HUVECs, which was closely associated with the expression levels of CXCL1(C-X-C Motif Chemokine Ligand 1), CXCL2(C-X-C Motif Chemokine Ligand 2), and CXCL8(C-X-C Motif Chemokine Ligand 8, also known as interleukin-8). At the same time, the results show that Toll Like Receptor 2 (TLR2) signaling pathway is activated and endoplasmic reticulum stress (ER stress) occurs. Furthermore, the findings revealed that the use of protein kinase RNA-like endoplasmic reticulum kinase (PERK) and Immunoglobulin-Regulated Enhancer 1 (IRE1) inhibitors reduced the expression levels of CXCL1, CXCL2, and CXCL8. Additionally, inhibiting TLR2 significantly decreased the expression levels of ER stress-related proteins (PERK and IRE1), CXCL1, CXCL2, and CXCL8. Consequently, neutrophil chemotaxis was significantly inhibited after treatment with TLR2, PERK, and IRE1 inhibitors. These findings shed light on the role of Tp0768 in enhancing neutrophil chemotaxis in endothelial cells, providing a foundation for further exploration of syphilis pathogenesis and offering a new direction for the diagnosis and treatment of T. pallidum infection.

Endothelial dysfunction of syphilis: Pathogenesis.

Treponema pallidum is the causative factor of syphilis, a sexually transmitted disease (STD) characterized by perivascular infiltration of inflammatory cells, vascular leakage, swelling and proliferation of endothelial cells (ECs). The endothelium lining blood and lymphatic vessels is a key barrier separating body fluids from host tissues and is a major target of T. pallidum. In this review, we focus on how T. pallidum establish intimate interactions with ECs, triggering endothelial dysfunction such as endothelial inflammation, abnormal repairment and damage of ECs. In addition, we summarize that migration and invasion of T. pallidum across vascular ECs may occur through two pathways. These two mechanisms of transendothelial migration are paracellular and cholesterol-dependent, respectively. Herein, clarifying the relationship between T. pallidum and endothelial dysfunction is of great significance to provide novel strategies for diagnosis and prevention of syphilis, and has a great potential prospect of clinical application.

Resurgence of syphilis: focusing on emerging clinical strategies and preclinical models.

Syphilis, a sexually transmitted disease (STD) caused by Treponema pallidum (T. pallidum), has had a worldwide resurgence in recent years and remains a public health threat. As such, there has been a great deal of research into clinical strategies for the disease, including diagnostic biomarkers and possible strategies for treatment and prevention. Although serological testing remains the predominant laboratory diagnostic method for syphilis, it is worth noting that investigations pertaining to the DNA of T. pallidum, non-coding RNAs (ncRNAs), chemokines, and metabolites in peripheral blood, cerebrospinal fluid, and other bodily fluids have the potential to offer novel perspectives on the diagnosis of syphilis. In addition, the global spread of antibiotic resistance, such as macrolides and tetracyclines, has posed significant challenges for the treatment of syphilis. Fortunately, there is still no evidence of penicillin resistance. Hence, penicillin is the recommended course of treatment for syphilis, whereas doxycycline, tetracycline, ceftriaxone, and amoxicillin are viable alternative options. In recent years, efforts to discover a vaccine for syphilis have been reignited with better knowledge of the repertoire of T. pallidum outer membrane proteins (OMPs), which are the most probable syphilis vaccine candidates. However, research on therapeutic interventions and vaccine development for human subjects is limited due to practical and ethical considerations. Thus, the preclinical model is ideal for conducting research, and it plays an important role in clinical transformation. Different preclinical models have recently emerged, such as in vitro culture and mouse models, which will lay a solid foundation for clinical treatment and prevention of syphilis. This review aims to provide a comprehensive summary of the most recent syphilis tactics, including detection, drug resistance treatments, vaccine development, and preclinical models in clinical practice.

Genomic epidemiology reveals early transmission of SARS-CoV-2 and mutational dynamics in Nanning, China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are a fatal pathogen resulting in substantial morbidity and mortality, and posing a great threat to human health with epidemics and pandemics. METHODS: Next-generation sequencing (NGS) was performed to investigate the SARS-CoV-2 genomic characterization. Phylogenetic analysis of SARS-CoV-2 genomes was used to probe the evolutionary. Homology protein structure modelling was done to explore potential effect of the mutations. RESULTS: The eighty genome sequences of SARS-CoV-2 obtained from the thirty-nine patients with COVID-19. A novel variant with mutation H625R concomitant with S50L in spike glycoprotein had been identified. Phylogenetic analysis revealed that SARS-CoV-2 variants belong to several distinct lineages. Homology modelling indicated that variant with mutation H625R and S50L increases flexibility of S1 subunit. CONCLUSIONS: SARS-CoV-2 genomes are constantly evolving by accumulation of point mutations. The amino acid H625R in combination with S50L may have a significant impact on the interaction between spike glycoprotein and ACE2.

Insight into the invasion process and immune-protective evaluation of Tp0971, a membrane lipoprotein from Treponema pallidum.

IMPORTANCE: The past two decades have seen a worldwide resurgence in infections caused by Treponema pallidum (T. pallidum) subsp. pallidum, the syphilis spirochete. The well-recognized capacity of the syphilis spirochete for early dissemination and immune evasion has earned it the designation "the stealth pathogen." There are many hurdles to studying syphilis pathogenesis, most notably the difficulty of culturing and genetically manipulating T. pallidum, as well as the absence of an effective vaccine for T. pallidum prevention. T. pallidum infection in humans is a complex and lengthy process. In this study, we investigated the invasion process and the function of the infection-dependent antigen Tp0971 as an immunogen to inhibit the dissemination of T. pallidum in an animal infection model. This enables a better understanding of the specific pathogenic mechanism of this pathogen, syphilis pathogenesis, and vaccine research.

Integrated Device Based on a Sudomotor Nanomaterial for Sweat Detection.

The compositions of sweat and blood are related. Therefore, sweat is an ideal noninvasive test body fluid that could replace blood for linear detection of many biomarkers, especially blood glucose. However, access to sweat samples remains limited to physical exercise, thermal stimulation, or electrical stimulation. Despite intensive research, a continuous, innocuous, and stable method for sweat stimulation and detection has not yet been developed. In this study, a nanomaterial for a sweat-stimulating gel based on the transdermal drug delivery system is presented, which transports acetylcholine chloride into the receptors of sweat glands to achieve the function of biological stimulation of skin sweating. The nanomaterial was applied to a suitable integrated sweat glucose detection device for noninvasive blood glucose monitoring. The total amount of evaporated sweat enabled by the nanomaterial is up to 35 µL·cm-2 for 24 h, and the device detects up to 17.65 µM glucose under optimal conditions, showing stable performance regardless of the user's activity level. In addition, the in vivo test was performed and compared with several studies and products, which showed excellent detection performance and osmotic relationship. The nanomaterial and associated integrated device represent a significant advance in continuous passive sweat stimulation and noninvasive sweat glucose measurement for point-of-care applications.

Immunization with Tp0954, an adhesin of Treponema pallidum, provides protective efficacy in the rabbit model of experimental syphilis.

Syphilis, a chronic multisystemic disease caused by spirochete Treponema pallidum subspecies pallidum infection, continues to be a serious global health problem and congenital syphilis remains a major cause of adverse outcomes in pregnancy in developing countries. The development of an effective vaccine is the most cost-effective way to eliminate syphilis, but so far has been elusive. Here, we evaluated the immunogenicity and protective efficacy of Tp0954, a T. pallidum placental adhesin, as a potential vaccine candidate in a New Zealand White rabbit model of experimental syphilis. Animals immunized with recombinant Tp0954 (rTp0954) produced high titers of Tp0954-specific serum IgG, high levels of IFN-γ from splenocytes and specific splenocyte proliferation response when compared to control animals immunized with PBS and Freund's adjuvant (FA). Furthermore, rTp0954 immunization significantly delayed the development of cutaneous lesions, promoted inflammatory cellular infiltration at the primary lesion sites, as well as inhibited T. pallidum dissemination to distal tissues or organs when compared with that of the control animals. In addition, the naïve rabbits receiving popliteal lymph nodes from Tp0954-immunized, T. pallidum-challenged animals were not infected by T. pallidum, confirming sterile immunity. These findings suggest that Tp0954 is a potential vaccine candidate against syphilis.

Treponema pallidum FlaA2 inducing the release of pro-inflammatory cytokines is mediated via TLR2 in keratinocytes.

BACKGROUND: Syphilis, caused by Treponema pallidum (T. pallidum), is a multi-organ, multiple systems, multi-stage sexually transmitted diseases with various clinical manifestations, among of which pathological lesions of skin and mucosa are the typical clinical manifestations of syphilis. However, the immunopathogenesis of this process is poorly understood. T. pallidum flagellin FlaA2, as a part of the important organelle responsible for the causative agent's motility, may contributes to the host skin inflammatory response. OBJECTIVES: To determine the mechanisms of T. pallidum FlaA2 stimulating the expression of pro-inflammatory cytokines in human keratinocytes. METHODS: Recombinant FlaA2 protein was performed to stimulate human keratinocytes. The mRNA transcription levels and protein expression levels of IL-6 and IL-8 were detected by qRT-PCR and ELISA, respectively. Western blot was used to detect the total protein and phosphorylation levels of ERK, p38, JNK and NF-κB, respectively. The intracellular location of NF-κB p65 was detected by immunofluorescence staining. RESULTS: Recombinant FlaA2 could considerably induced the expression of pro-inflammation cytokines IL-6 and IL-8 in HaCaT cells, and FlaA2-induced IL-6 and IL-8 secretion could be decreased by inhibiting TLR2 using pZERO-hTLR2. Further investigation showed that FlaA2 could activate the phosphorylation of ERK, p38 and IκBα and FlaA2-stimulated secretion of IL-6, IL-8 were attenuated by ERK, p38 and NF-κB inhibitors in HaCaT cells. Moreover, FlaA2 activates the ERK, p38 and NF-κB pathways through TLR2 signaling pathway in HaCaT cells. CONCLUSIONS: From the findings above, these results confirm that T. pallidum FlaA2 activates ERK, p38 and NF-κB signaling pathway through TLR2 pathway to induce the production of IL-6 and IL-8, which could contribute to enhance the understanding of the skin inflammatory response induced by the pathogen in syphilis patients.

Viral Dynamic Surveillance in COVID-19 Patients: A Cohort Study.

Background: Coronavirus disease 2019 (COVID-19) is a potentially fatal pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially those of novel SARS-CoV-2 variants and infection has affected over 700 million people globally. Methods: This retrospective, descriptive study included 118 patients admitted with SARS-CoV-2 infection as confirmed by real-time reverse transcription polymerase chain reaction. Results: The median duration of detectable SARS-CoV-2 infection in patients with high ALT, AST, and PLT/LYMPH, or low CD4+, CD8+, and PLT/MONO was considerably longer. In the risk factor model, multivariate analysis was performed for the estimation of ALT (HR, 0.54; 95% CI, 0.36-0.81), AST (HR, 0.56; 95% CI, 0.34-0.93), CD4+ (HR,0.77; 95% CI, 0.48-1.24), CD8+ (HR,0.64; 95% CI, 0.37-1.11), PLT/LYMPH (HR, 1.16; 95% CI, 0.76-1.77), and PLT/MONO (HR, 0.64; 95% CI, 0.43-0.94). Conclusions: The longer viral RNA duration was associated with a higher International Prognostic Index score (p = 0.0013), demonstrating for the first time that multivariate features of the bioindicators closely associated with SARS-CoV-2-infected patients clear the virus.

Assessment of recombinant antigens Tp0100 and Tp1016 of Treponema pallidum for serological diagnosis of syphilis.

OBJECTIVE: To discover novel serodiagnostic candidates for the serological diagnosis of syphilis. METHODS: Two recombinant Treponema pallidum proteins Tp0100 and Tp1016 were expressed, purified, and identified by Western Blotting. A total of 600 clinical serum samples were tested with the Tp0100-based ELISA, the Tp1016-based ELISA, and the commercial LICA Syphilis TP kit (ChIVD, Beijing, China). The sensitivities were determined by testing 340 samples from individuals with clinically diagnosed primary, secondary, latent, and tertiary syphilis. The specificities were determined by screening 260 samples from healthy controls and individuals with potentially cross-reactive infections, including leptospirosis, Lyme disease, hepatitis B, tuberculosis, rheumatoid arthritis, systemic lupus erythematosus. Kappa (κ) values were applied to compare the agreement between clinical syphilis diagnosis and the Tp0100-based ELISA, the Tp1016-based ELISA, or the LICA Syphilis TP test. RESULTS: Using clinical syphilis diagnosis as the gold standard, Tp0100 exhibited an overall sensitivity of 95.6% and specificity of 98.1% for testing IgG antibody while Tp1016 demonstrated only an overall sensitivity of 75.0% and specificity of 79.6%. In contrast, the LICA Syphilis TP test revealed an overall sensitivity of 97.6% and specificity of 96.2%. In addition, the overall percent agreement and corresponding κ values were 96.7% (95% CI 95.6%-97.8%) and 0.93 for the Tp0100-based ELISA, 77.0% (95% CI 74.3%-79.7%) and 0.54 for the Tp1016-based ELISA, and 97.0% (95% CI 96.0%-98.0%) and 0.94 for the LICA Syphilis TP test, respectively. CONCLUSION: The recombinant T. pallidum protein Tp0100 shows promise as a novel diagnostic antigen in the serological tests for syphilis.

Possible effects of Treponema pallidum infection on human vascular endothelial cells.

Pathogens can affect host cells in various ways, and the same effect can be found in the Treponema pallidum acting on the endothelium of host vessels, and the mechanism is often complex and multiple. Based on the existing T. pallidum of a cognitive framework, the first concerns involving T. pallidum or the bacteria protein directly acted on vascular endothelial cells of the host, the second concerns mainly involved in the process of T. pallidum infection in vivo blood lipid change, secretion of cytokines and the interactions between immune cells indirectly. Through both direct and indirect influence, this study explores the role of host by T. pallidum infect in the process of the vascular endothelium.

Painless and sensitive pepsinogen I detection: an electrochemical immunosensor based on rhombic dodecahedral Cu3Pt and MoS2 NFs.

Gastric cancer (GC) is a common malignant tumour of the digestive tract with a high mortality rate worldwide. However, many patients delay treatment due to the avoidance of the costly and painful procedure of gastroscopy. Therefore, an early convenient screening method is essential to improve the survival rate of GC patients. To address this issue, we constructed an electrochemical immunosensor supported by rhombohedral Cu3Pt and MoS2 nanoflowers (MoS2 NFs) for rapid, painless and quantitative detection of the GC biomarker in vitro. Here, pepsinogen I was employed as a model protein biomarker to analyse the performance of the immunosensor. The rhombohedral dodecahedral Cu3Pt nanoparticles decorated with MoS2-NFs were further functionalized; this allowed the constructed sensor to possess more nano- or micro-structures, thereby improving the detection sensitivity. In specific applications, the corresponding bioactive molecules can be flexibly captured. Under optimal conditions, the immunoassay showed a wide linear range from 500 pg mL-1 to 400 ng mL-1 and a low detection limit of 167 pg mL-1 (S/N = 3). This covers the critical value of 70 ng mL-1, and the results obtained from the analysis of human serum samples were on par with those from the enzyme immunoassay, suggesting significant potential for this new method in daily diagnosis.

Two Potential Syphilis Vaccine Candidates Inhibit Dissemination of Treponema pallidum.

Syphilis, caused by the spirochete Treponema pallidum subspecies pallidum, continues to be a major public health problem worldwide. Recent increases in the number of syphilis cases, in addition to the lack of an efficient vaccine against T. pallidum for humans, highlights an urgent need for the design and development of an efficacious syphilis vaccine. Here, we assess the vaccine potential of the adhesion protein Tp0136 and the outer membrane protein Tp0663. Rabbits were subcutaneously immunized with recombinant proteins Tp0136, Tp0663, or control PBS. Immunization with Tp0136 or Tp0663 generated a strong humoral immune response with high titers of IgG, as assessed by ELISA. Moreover, animals immunized with Tp0136 or Tp0663 exhibited attenuated lesion development, increased cellular infiltration at the lesion sites, and inhibition of treponemal dissemination to distant organs compared to the unimmunized animals. These findings indicate that Tp0136 and Tp0663 are promising syphilis vaccine candidates. Furthermore, these results provide novel and important information for not only understanding the pathogenic mechanisms of spirochetes, but also the development of spirochete-specific subunit vaccines.

A rapid lateral flow immunoassay strip for detection of SARS-CoV-2 antigen using latex microspheres.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious and concealed virus that causes pneumonia, severe acute respiratory syndrome, and even death. Although the epidemic has been controlled since the development of vaccines and quarantine measures, many people are still infected, particularly in third-world countries. Several methods have been developed for detection of SARS-CoV-2, but owing to its price and efficiency, the immune strip could be a better method for the third-world countries. METHODS: In this study, two antibodies were linked to latex microspheres, using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide, as the bridge to decrease the cost further and improve the detection performance. The specificity of the lateral flow immunoassay strip (LFIA) was tested by several common viruses and respiratory bacterial infections. Besides, the reproducibility and stability of the LFIAs were tested on the same batch of test strips. Under optimal conditions, the sensitivity of LFIA was determined by testing different dilutions of the positive specimens. RESULTS: The proposed LFIAs were highly specific, and the limit of detection was as low as 25 ng/mL for SARS-CoV-2 antigens. The clinical applicability was evaluated with 659 samples (230 positive and 429 negative samples) by using both LFIA and rRT-PCR. Youden's index (J) was used to assess the performance of these diagnostic tests. The sensitivity and specificity were 98.22% and 97.93%, respectively, and J is 0.9615. The sensitivity and specificity were 98.22% and 97.93%, respectively, and J is 0.9615. In addition, the consistency of our proposed LFIA was analyzed using Cohen's kappa coefficient (κ = 0.9620). CONCLUSION: We found disease stage, age, gender, and clinical manifestations have only a slight influence on the diagnosis. Therefore, the lateral flow immunoassay SARS-CoV-2 antigen test strip is suitable for point-of-care detection and provides a great application for SARS-CoV-2 epidemic control in the third-world countries.

Recombinant Treponema pallidum protein Tp0768 promotes proinflammatory cytokine secretion of macrophages through ER stress and ROS/NF-κB pathway.

In response to danger signals, macrophages rapidly produce many inflammatory cytokines that trigger the cascade release of inflammatory mediators, leading to tissue damage, which is an important cause of clinical manifestations of syphilis at all stages. However, we still know very little about the specific mechanism of this process. Tp0768 is an infection-stage-dependent antigen that plays an important role in the infection of Treponema pallidum. In this study, we demonstrated that Tp0768 stimulation of macrophages can cause IL-1ß, IL-6, and IL-8 mRNA expression levels to increase in a dose- and time-dependent manner. Further research showed that Tp0768 activated ER stress and the ROS/NF-κB pathway in macrophages. Inhibition of ER stress and the ROS/NF-κB pathway inhibited the expression of IL-1ß, IL-6, and IL-8 induced by Tp0768. In addition, pretreatment with a PERK pathway inhibitor significantly reduced the expression of the NF-κB and JNK pathways, while also downregulating the expression of IL-1ß, IL-6, and IL-8. Tp0768 stimulation can activate IRE1α/XBP-1 signaling and participate in the induction of inflammatory cytokines through the JNK pathway. These findings indicate that Tp0768 promotes the secretion of proinflammatory cytokines IL-1ß, IL-6, and IL-8 by macrophages through ER stress and the ROS/NF-κB pathway, which are also involved in the activation of the NF-κB and JNK pathways that are induced by the PERK pathway and activation of IRE1α/XBP-1 signaling. KEY POINTS: • This study found for the first time that the recombinant Treponema pallidum protein Tp0768 promotes the production of IL-1ß, IL-6, and IL-8 by macrophages through ER stress. • Recombinant Treponema pallidum protein Tp0768 regulates the ROS/NF-κB pathway through ER stress. • ER stress-related pathway PERK induces the expression of IL-1ß, IL-6, and IL-8 by activating the NF-κB pathway and the JNK pathway. • IRE1α can induce the splicing of XBP-1mRNA and activate the JNK pathway.

Electrochemical immunosensor based on binary nanoparticles decorated rGO-TEPA as magnetic capture and Au@PtNPs as probe for CEA detection.

Using gold and magnetic nanoparticles co-decorated reduced graphene oxide-tetraethylenepentamine (rGO-TEPA/Au-MNPs) as the magnetic platform for capturing the primary antibody (Ab1), separation and preconcentration of immunocomplex, a novel homogeneous electrochemical immunosensor was successfully developed. The newly prepared magnetic rGO-TEPA/Au-MNPs, compared with MNPs, exhibited better stability and enhanced electrical conductivity attributed to rGO-TEPA, and showed higher biorecognition efficiency due to AuNPs. In addition, Au@PtNPs were prepared and modified with secondary antibody (Ab2) as an efficient signal probe for signal readout. Using carcinoembryonic antigen (CEA) as a model analyte, the prepared immunosensor demonstrated satisfactory properties like high stability, good repeatability and selectivity, wide linear range (5.0 pg mL-1~200.0 ng mL-1) as well as low detection limit (1.42 pg mL-1). The homogenous electrochemical immunosensor was applied to the detection of CEA in human serum and was found to exhibit good correlation with the reference method. Thus, the proposed rGO-TEPA/Au-MNPs-based homogenous immunoassay platform might open up a new way for biomarker diagnosis. Graphical Abstract.

Identification of key genes and pathways in syphilis combined with diabetes: a bioinformatics study.

We noticed that syphilis patients seem to be more susceptible to diabetes and the lesions often involve the kidneys, but the pathogenesis is not yet completely understood. In this study, microarray analysis was performed to investigate the dysregulated expressed genes (DEGs) in rabbit model of syphilis combined with diabetes. A total of 1045 genes were identified to be significantly differentially expressed, among which 571 were up-regulated and 474 were down-regulated (≥ 2.0fold, p < 0.05). Using the database visualization and integration discovery for the Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis. The downregulated DEGs were significantly enriched for biosynthesis of antibiotics, carbon metabolism and protein digestion, while the upregulated DEGs were mainly enriched for cancer and PI3K-Akt signaling pathway. Molecular Complex Detection (MCODE) plugins were used to visualize protein-protein interaction (PPI) network of DEGs and Screening for hub genes and gene modules. ALB, FN1, CASP3, MMP9, IL8, CTGF, STAT3, IGF1, VCAM-1 and HGF were filtrated as the hub genes according to the degree of connectivity from the PPI network. To the best of our knowledge, this study is the first to comprehensively identify the expression patterns of dysregulated genes in syphilis combined with diabetes, providing a basis for revealing the underlying pathogenesis of syphilis combined with diabetes and exploring the goals of therapeutic intervention.

Research status and perspectives for pathogenic spirochete vaccines.

Leptospira interrogans, Borrelia burgdorferi, and Treponema pallidum are important pathogenic spirochetes. The incidence of human diseases caused by pathogenic spirochetes, e.g., leptospirosis, Lyme disease, and syphilis, has been recently increased, posing a threat to public health. Mechanisms of spirochete pathogenicity are not yet fully understood, and no safe and effective vaccine to prevent and control the infection by pathogenic spirochetes is currently available. In this article, we review the progress of research into the pathogenic spirochete vaccine, mainly in terms of vaccine types. The development of relevant vaccines against pathogenic spirochetes has generally proceeded via several stages, such as the whole-cell inactivated vaccine, live attenuated vaccine, and gene-engineered vaccine, and will likely enter a new stage with the application of gene editing technology. In this review, we mainly summarized the types of pathogenic spirochete vaccines and conducted a preliminary analysis on the protective effect of immunity, and proposed a further prospect for the development of pathogenic spirochete vaccines.

A comparison of genotyping tool in Treponema pallidum: Review and meta-analysis.

BACKGROUND: To decipher the molecular epidemiology of the Treponema pallidum subspecies, pallidum, researchers have developed different molecular typing schemes which identify strains type from clinical specimens. However, the results of these studies show remarkable diversity. METHODS: We searched for literature in PubMed, MEDLINE, Web of Sciences, and OVID from January 1998 to January 2019, in order to compare the efficiency of typing schemes using published evidence for systematic reviews and meta-analyses. RESULTS: From the 43 studies included, the overall typing efficiency of Treponema pallidum was 71.4% (95% CI: 63.2-78.9%). Subgroup analyses indicated that the typing efficiency of CDC-typing (CDCT, 68.2%, 95% CI: 53.6-81.2%) was worse than those of enhanced CDC-typing (ECDCT, 72.3%, 95% CI: 60-83.1%), CDC-rspA (81.6%, 95% CI: 76.1-86.6%), multi-locus sequence typing (MLST, 67.1%, 95% CI: 61.1-72.7), and sequencing-based molecular typing (SBMT, 71.6%, 95% CI: 50-89.2%). A limitation of this review is that the studies included employed different criteria to collect and investigate samples of Treponema pallidum, which could contribute to heterogeneity. CONCLUSIONS: This analysis suggests that CDCT is an inferior scheme in molecular typing, the discriminatory power was very similar for ECDCT and SBMT. Other factors contributing to the heterogeneity between typing studies warrants further study.

HIV-induced cancer--all paths leading to Rome.

BACKGROUND: Although several viruses have been proved to induce host specific microRNAs (miRNAs, miRs), the expression of functional miRNAs induced by Human Immunodeficiency Virus 1 (HIV-1) infection is still unknown. The variation of the expression of HIV-1 inducing miRNAs both in vitro and in vivo (in all types of infected patient groups) implies that these specific miRNAs have potential roles in the development of diseases. However, few researches have noticed the roles of these serum miRNAs. In this study, we attempted to establish a macrocontrol regulation system and simulate the influence of HIV-1 inducing miRNAs during the development of cancer. METHODS: The miRbase, FunRich software, miRtarbase, STRING, TargetScanhuman, Cytoscape plugin ClueGO/Cluepedia/STRING, DAVID Bioinformatics Resources and GEO database were comprehensively employed in this bioinformatics study. RESULTS: The miRNAs in the serum of AIDS patients and its target genes have different expression levels in serum, an array of which are associated with cancer and metabolism signaling pathways. Moreover, the emerging role of miRNAs in HIV-1 infection is also involved in human cancer, using TCGA data integrative analysis. CONCLUSIONS: Therefore, we infer that serum miRNAs in HIV-1 infection may play important roles in HIV-induced cancer and could be used as a potential biomarker for HIV-cancers detection.