The impact of maxillary dimensions on determining surgical approach of fungal ball in the maxillary sinus.

Endoscopic middle meatal antrostomy (MMA) is commonly used for maxillary sinus (MS) fungal ball removal. For challenging cases involving anterior or inferior recess, an additional inferior meatal approach (IMA) might be needed. We analyzed the differences in MS dimensions on CT scans according to the surgical approach to suggest preoperative variables that could facilitate an additional IMA. CT scans of 281 adult patients who underwent ESS for the MS fungal ball (139 MMA, 62 MMA & IMA) were evaluated for comparative analysis of 8 MS measurements based on the surgical approach. Complete removal was achieved in all cases. Age and sex didn't differ significantly (p > 0.05). The maximum distances between the anterior-posterior walls, the inferior ostium border to the lateral recess, and the ostium to the inferior wall of the MS were statistically greater in the MMA & IMA group compared to the MMA group (p = 0.003, p = 0.005, and p = 0.010, respectively), especially among females. This study underscores the clinical importance of specific measurements-anterior to posterior wall, medial wall to lateral recess, and ostium to inferior wall of the maxillary sinus-for guiding optimal surgical approaches in MS lesions.

CM1, a Chrysin Derivative, Protects from Endotoxin-Induced Lethal Shock by Regulating the Excessive Activation of Inflammatory Responses.

Sepsis, a leading cause of death worldwide, is a harmful inflammatory condition that is primarily caused by an endotoxin released by Gram-negative bacteria. Effective targeted therapeutic strategies for sepsis are lacking. In this study, using an in vitro and in vivo mouse model, we demonstrated that CM1, a derivative of the natural polyphenol chrysin, exerts an anti-inflammatory effect by inducing the expression of the ubiquitin-editing protein TNFAIP3 and the NAD-dependent deacetylase sirtuin 1 (SIRT1). Interestingly, CM1 attenuated the Toll-like receptor 4 (TLR4)-induced production of inflammatory cytokines by inhibiting the extracellular-signal-regulated kinase (ERK)/MAPK and nuclear factor kappa B (NF-κB) signalling pathways. In addition, CM1 induced the expression of TNFAIP3 and SIRT1 on TLR4-stimulated primary macrophages; however, the anti-inflammatory effect of CM1 was abolished by the siRNA-mediated silencing of TNFAPI3 or by the genetic or pharmacologic inhibition of SIRT1. Importantly, intravenous administration of CM1 resulted in decreased susceptibility to endotoxin-induced sepsis, thereby attenuating the production of pro-inflammatory cytokines and neutrophil infiltration into the lung compared to control mice. Collectively, these findings demonstrate that CM1 has therapeutic potential for diverse inflammatory diseases, including sepsis.

E-cigarettes exacerbate allergic inflammation via cytokine induction and MUC5AC/5B expression in a murine asthma model.

The effects of electronic cigarettes (e-cigarettes) vapor on inflammation and mucin secretion on asthmatics remain insufficiently explored. This study investigated the effects of e-cigarette vapor on allergic inflammation, cytokine production, and MUC5AC/5B expression in murine asthma model. Airway hyperresponsiveness was significantly higher in the e-cigarette-exposed ovalbumin (OVA) sensitization group than in the control, e-cigarette exposure, and OVA sensitization groups. The e-cigarette-exposed OVA sensitization group showed significantly greater infiltration of inflammatory cells and Th2-mediated inflammatory cytokines (interleukin-4 and -5) compared to the control, e-cigarette exposure, and OVA sensitization groups. MUC5AC mucin levels were significantly elevated in the e-cigarette exposure, OVA sensitization, and e-cigarette-exposed OVA sensitization groups, whereas MUC5B mucin levels were significantly elevated in the OVA sensitization and e-cigarette-exposed OVA sensitization groups. The results may suggest that the exposure to e-cigarette vapor in an asthmatics promoted allergic inflammation and increased mucin secretion, ultimately leading to the exacerbation of asthma.

Positive airway pressure therapy compliance in patients with comorbid insomnia and sleep apnea (COMISA).

Objectives: This study aimed to compare positive airway pressure (PAP) therapy compliance between patients with comorbid insomnia and sleep apnea (COMISA) and those with obstructive sleep apnea (OSA) alone, while assessing the influence of insomnia clinic visits on PAP compliance. Methods: Patients diagnosed with OSA and initiated on PAP therapy between January 2012 and December 2021 were included. The COMISA group (n = 43) comprised patients with insomnia, while the control group (n = 86) consisted of OSA patients without insomnia, matched 1:2 based on age and sex. COMISA patients were further categorized into Group A (n = 20) with at least two insomnia clinic visits and Group B (n = 23) with minimal or no visits. PAP compliance was evaluated for each group at 3 and 9 months. Results: No significant differences were observed in PAP compliance between COMISA patients and OSA patients without insomnia. Within the COMISA group, the impact of insomnia clinic visits on PAP compliance was not significant. No significant difference was observed in the daily PAP usage between the two groups at 3 months (265.5 ± 145.9 min in Group A vs. 236.3 ± 152.3 min in Group B, p = 0.760) or 9 months (213.4 ± 155.3 min in Group A vs. 166.3 ± 158.3 min in Group B, p = 0.538). Percentages of PAP users and nights with PAP use exceeding 4 hours also showed no significant differences at both intervals. Conclusion: This study demonstrated no significant disparity in PAP compliance between the COMISA and control groups at either 3 or 9 months. Furthermore, insomnia clinic visits did not significantly impact PAP compliance in COMISA patients during the 3- and 9-month intervals.

Safety and efficacy of a novel anti-CD19 chimeric antigen receptor T cell product targeting a membrane-proximal domain of CD19 with fast on- and off-rates against non-Hodgkin lymphoma: a first-in-human study.

BACKGROUND: Commercial anti-CD19 chimeric antigen receptor T-cell therapies (CART19) are efficacious against advanced B-cell non-Hodgkin lymphoma (NHL); however, most patients ultimately relapse. Several mechanisms contribute to this failure, including CD19-negative escape and CAR T dysfunction. All four commercial CART19 products utilize the FMC63 single-chain variable fragment (scFv) specific to a CD19 membrane-distal epitope and characterized by slow association (on) and dissociation (off) rates. We hypothesized that a novel anti-CD19 scFv that engages an alternative CD19 membrane-proximal epitope independent of FMC63 and that is characterized by faster on- and off-rates could mitigate CART19 failure and improve clinical efficacy. METHODS: We developed an autologous CART19 product with 4-1BB co-stimulation using a novel humanized chicken antibody (h1218). This antibody is specific to a membrane-proximal CD19 epitope and harbors faster on/off rates compared to FMC63. We tested h1218-CART19 in vitro and in vivo using FMC63-CART19-resistant models. We conducted a first-in-human multi-center phase I clinical trial to test AT101 (clinical-grade h1218-CART19) in patients with relapsed or refractory (r/r) NHL. RESULTS: Preclinically, h1218- but not FMC63-CART19 were able to effectively eradicate lymphomas expressing CD19 point mutations (L174V and R163L) or co-expressing FMC63-CAR19 as found in patients relapsing after FMC63-CART19. Furthermore, h1218-CART19 exhibited enhanced killing of B-cell malignancies in vitro and in vivo compared with FMC63-CART19. Mechanistically, we found that h1218-CART19 had reduced activation-induced cell death (AICD) and enhanced expansion compared to FMC63-CART19 owing to faster on- and off-rates. Based on these preclinical results, we performed a phase I dose-escalation trial, testing three dose levels (DL) of AT101 (the GMP version of h1218) using a 3 + 3 design. In 12 treated patients (7 DLBCL, 3 FL, 1 MCL, and 1 MZL), AT101 showed a promising safety profile with 8.3% grade 3 CRS (n = 1) and 8.3% grade 4 ICANS (n = 1). In the whole cohort, the overall response rate was 91.7%, with a complete response rate of 75.0%, which improved to 100% in DL-2 and -3. AT101 expansion correlates with CR and B-cell aplasia. CONCLUSIONS: We developed a novel, safe, and potent CART19 product that recognizes a membrane-proximal domain of CD19 with fast on- and off-rates and showed significant efficacy and promising safety in patients with relapsed B-cell NHL. TRIAL REGISTRATION: NCT05338931; Date: 2022-04-01.

Toxoplasma gondii Induces Pyroptosis in Human Placental Trophoblast and Amniotic Cells by Inducing ROS Production and Activation of Cathepsin B and NLRP1/NLRP3/NLRC4/AIM2 Inflammasome.

Toxoplasma gondii infection in pregnant women may cause fetal anomalies; however, the underlying mechanisms remain unclear. The current study investigated whether T. gondii induces pyroptosis in human placental cells and the underlying mechanisms. Human placental trophoblast (BeWo and HTR-8/SVneo) and amniotic (WISH) cells were infected with T. gondii, and then reactive oxygen species (ROS) production, cathepsin B (CatB) release, inflammasome activation, and pyroptosis induction were evaluated. The molecular mechanisms of these effects were investigated by treating the cells with ROS scavengers, a CatB inhibitor, or inflammasome-specific siRNA. T. gondii infection induced ROS generation and CatB release into the cytosol in placental cells but decreased mitochondrial membrane potential. T. gondii-infected human placental cells and villi exhibited NLRP1, NLRP3, NLRC4, and AIM2 inflammasome activation and subsequent pyroptosis induction, as evidenced by increased expression of ASC, cleaved caspase-1, and mature IL-1ß and gasdermin D cleavage. In addition to inflammasome activation and pyroptosis induction, adverse pregnancy outcome was shown in a T. gondii-infected pregnant mouse model. Administration of ROS scavengers, CatB inhibitor, or inflammasome-specific siRNA into T. gondii-infected cells reversed these effects. Collectively, these findings show that T. gondii induces NLRP1/NLRP3/NLRC4/AIM2 inflammasome-dependent caspase-1-mediated pyroptosis via induction of ROS production and CatB activation in placental cells. This mechanism may play an important role in inducing cell injury in congenital toxoplasmosis.

Limited Palatal Muscle Resection for the Treatment of Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis.

Background and Objectives: Limited palatal muscle resection (PMR) is a surgical technique employed to alleviate respiratory disturbances in obstructive sleep apnea (OSA) patients with retropalatal narrowing by reducing soft palate volume and tightening the muscles. Although some previous publications have demonstrated the effectiveness of limited PMR, the overall efficacy and therapeutic role of limited PMR for the treatment of OSA remain uncertain. This study utilized meta-analysis and a systematic literature review to estimate the overall effectiveness of limited PMR in treating OSA. Materials and Methods: Multiple databases, including PubMed, EMBASE, Cochrane Library, and Web of Science, were searched using specific keywords related to OSA and limited PMR. Original articles assessing respiratory disturbances before and after limited PMR in patients with OSA were included. Data from selected articles were collected using standardized forms, including clinicodemographic characteristics, apnea-hypopnea index (AHI), and lowest pulse oximetry values (minimum SpO2). Random effect models were used for analyzing significant heterogeneity. Egger's test and funnel plot were used to identify publication bias. Results: Four studies were included in this meta-analysis for AHI, and three studies were included for minimum SpO2 during sleep. A significant reduction in the AHI and an increase in the minimum SpO2 were shown following limited PMR as the standardized mean difference (95% confidence interval) was 2.591 (1.092-4.090) and 1.217 (0.248-2.186), respectively. No publication bias was found in either analysis. Conclusions: The results of the meta-analysis and systemic review add to the literature that limited PMR can result in a reduction in the AHI and an increase in min SaO2. In OSA patients with suspected retropalatal obstruction, limited PMR may be efficiently performed.

Drainage of a Pterygopalatine Fossa Abscess With Chronic Sinusitis via an Endoscopic Nasal Approach.

The pterygopalatine fossa is a clinically inaccessible space deep in the face, and reports of pterygopalatine fossa abscesses are rare. The authors present the case of a 63-year-old woman presenting with a severe headache owing to an abscess involving the pterygopalatine fossa. On a computed tomography scan, inflammation of the right pterygopalatine fossa associated with right maxillary sinusitis and periapical inflammation and a cystic lesion around the tooth were observed. After administering appropriate antibiotics, the headache improved considerably, and endoscopic nasal surgery resulted in adequate abscess drainage. To the authors' knowledge, this case study is one of the few reporting the successful treatment of an abscess in the pterygopalatine fossa through an endoscopic transnasal approach.

Expression of cytokines and co-stimulatory molecules in the Toxoplasma gondii-infected dendritic cells of C57BL/6 and BALB/c mice.

Toxoplasma gondii is an intracellular protozoan parasite which can infect most warm-blooded animals and humans. Among the different mouse models, C57BL/6 mice are more susceptible to T. gondii infection compared to BALB/c mice, and this increased susceptibility has been attributed to various factors, including T-cell responses. Dendritic cells (DCs) are the most prominent type of antigen-presenting cells and regulate the host immune response, including the response of T-cells. However, differences in the DC responses of these mouse strains to T. gondii infection have yet to be characterized. In this study, we cultured bone marrow-derived DCs (BMDCs) from BALB/c and C57BL/6 mice. These cells were infected with T. gondii. The activation of the BMDCs was assessed based on the expression of cell surface markers and cytokines. In the BMDCs of both mouse strains, we detected significant increases in the expression of cell surface T-cell co-stimulatory molecules (major histocompatibility complex (MHC) II, CD40, CD80, and CD86) and cytokines (tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-12p40, IL-1ß, and IL-10) from 3 h post-T. gondii infection. The expression of MHC II, CD40, CD80, CD86, IFN-γ, IL-12p40, and IL-1ß was significantly higher in the T. gondii-infected BMDCs obtained from the C57BL/6 mice than in those from the BALB/c mice. These findings indicate that differences in the activation status of the BMDCs in the BALB/c and C57BL/6 mice may account for their differential susceptibility to T. gondii.

Association between poly-sensitisation and sensitisation to staphylococcal enterotoxin A and B affecting allergic severity in children.

PURPOSE: Accumulating evidence suggests that Staphylococcus aureus plays a significant role as a disease modifier in upper and lower airway diseases. We aimed to assess the association between staphylococcal enterotoxins (SEs) with allergic diseases and the degree of allergen sensitisation in children, which remains unclear. METHODS: We retrospectively reviewed the medical records of 455 patients aged 3-18 years between March 2018 and March 2022. Clinical history and demographic data were obtained. The baseline study included paranasal sinus X-ray scan, multiple allergen simultaneous test, and ImmunoCAP® for measuring serum total and specific immunoglobulin E (IgE) levels to allergens and staphylococcal enterotoxin A and B (SEA and SEB). RESULTS: The mean age was 9.77 ± 4.3 years. 133 patients (29.2%) were sensitised to one inhalant allergen, and 188 patients (41.3%) showed polysensitisation. Patients sensitised to SEs showed higher total and specific IgE levels and total eosinophil counts compared to non-SE-sensitised patients. Sensitisation to SEs is closely associated with polysensitisation to inhalant allergens and allergic multimorbidity. When the SE-IgE value was 0.35 or higher, the odds ratio for allergen polysensitisation was significantly higher than when the SE-IgE value was lower than 0.35. CONCLUSIONS: Association between polysensitisation and sensitisation to SEs in children shows the higher the specific IgE levels for SEs, the higher the likelihood of polysensitisation. Considering the relationship between polysensitisation, high IgE levels, and the severity of allergic morbidity, sensitisation to SEs is thought to be related to allergy severity.

Recombinant AMA1 Virus-like Particle Antigen for Serodiagnosis of Toxoplasma gondii Infection.

Toxoplasmosis diagnosis predominantly relies on serology testing via enzyme-linked immunosorbent assay (ELISA), but these results are highly variable. Consequently, various antigens are being evaluated to improve the sensitivity and specificity of toxoplasmosis serological diagnosis. Here, we generated Toxoplasma gondii virus-like particles displaying AMA1 of T. gondii and evaluated their diagnostic potential. We found that AMA1 VLPs were highly sensitive and reacted with the sera acquired from mice infected with either T. gondii ME49 or RH strains. The overall IgG and IgM antibody responses elicited by AMA1 VLPs were substantially higher than those induced by the conventionally used T. gondii lysate antigen (TLA). Importantly, AMA1 VLPs were capable of detecting parasitic infection with T. gondii RH and ME49 as early as 1 week post-infection, even when mice were exposed to low infectious doses (5 × 103 and 10 cysts, respectively). AMA1 VLPs also did not cross-react with the immune sera acquired from Plasmodium berghei-infected mice. Compared to TLA, stronger antibody responses were induced by AMA1 VLPs when tested using T. gondii-infected human sera. The sensitivities and specificities of the two antigens were substantially different, with AMA1 VLPs demonstrating over 90% sensitivity and specificity, whereas these values were in the 70% range for the TLA. These results indicated that AMA1 VLPs can detect infections of both T. gondii ME49 and RH at an early stage of infection caused by very low infection doses in mice, and these could be used for serological diagnosis of human toxoplasmosis.

SIRT1 Promotes Host Protective Immunity against Toxoplasma gondii by Controlling the FoxO-Autophagy Axis via the AMPK and PI3K/AKT Signalling Pathways.

Sirtuin 1 (SIRT1) regulates cellular processes by deacetylating non-histone targets, including transcription factors and intracellular signalling mediators; thus, its abnormal activation is closely linked to the pathophysiology of several diseases. However, its function in Toxoplasma gondii infection is unclear. We found that SIRT1 contributes to autophagy activation via the AMP-activated protein kinase (AMPK) and PI3K/AKT signalling pathways, promoting anti-Toxoplasma responses. Myeloid-specific Sirt1-/- mice exhibited an increased cyst burden in brain tissue compared to wild-type mice following infection with the avirulent ME49 strain. Consistently, the intracellular survival of T. gondii was markedly increased in Sirt1-deficient bone-marrow-derived macrophages (BMDMs). In contrast, the activation of SIRT1 by resveratrol resulted in not only the induction of autophagy but also a significantly increased anti-Toxoplasma effect. Notably, SIRT1 regulates the FoxO-autophagy axis in several human diseases. Importantly, the T. gondii-induced phosphorylation, acetylation, and cytosolic translocation of FoxO1 was enhanced in Sirt1-deficient BMDMs and the pharmacological inhibition of PI3K/AKT signalling reduced the cytosolic translocation of FoxO1 in BMDMs infected with T. gondii. Further, the CaMKK2-dependent AMPK signalling pathway is responsible for the effect of SIRT1 on the FoxO3a-autophagy axis and for its anti-Toxoplasma activity. Collectively, our findings reveal a previously unappreciated role for SIRT1 in Toxoplasma infection.

Crushed Septal Cartilage-Covered Diced Cartilage Glue (CCDG) Graft: A Hybrid Technique of Crushed Septal Cartilage.

BACKGROUND: Diced cartilage glue (DG) grafts have been widely used in dorsal augmentation but can induce dorsal irregularities. The authors evaluated the postoperative feasibility of a crushed septal cartilage-covered diced cartilage glue (CCDG) graft. METHODS: The medical records of 38 patients who underwent dorsal augmentation rhinoplasty with an open approach were retrospectively reviewed. DG graft was used in 18 patients (47.4%), and CCDG graft was used in 20 patients (52.6%). Surgical outcomes were assessed by comparing anthropometric data on facial photographs and satisfaction questionnaires on aesthetic outcomes and palpable irregularities on nasal dorsum before and after surgery. RESULTS: Both groups showed successful aesthetic outcomes. Dorsal height, radix height, and tip projection were all increased postoperatively in both groups. Tip rotation did not significantly increase (p > 0.05). Both groups showed similar outcomes in terms of aesthetic satisfaction but a significant difference in palpable irregularity. CCDG graft group showed significantly better (p = 0.04) satisfaction with dorsal irregularities (4.15 ± 0.75) than the DG graft group (3.56 ± 0.92). CCDG graft group also showed significantly better mean values (p = 0.048) in the degree of irregularity by two surgeons (3.85 ± 0.65) than the DG graft group (3.25 ± 0.97). No patient had significant complaints about irregular dorsum, and none of them underwent a revision rhinoplasty. CONCLUSION: CCDG graft can be a complementary option for avoiding postoperative irregular dorsum complications. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .

Trichomonas vaginalis induces apoptosis via ROS and ER stress response through ER-mitochondria crosstalk in SiHa cells.

BACKGROUND: Trichomonas vaginalis causes lesions on the cervicovaginal mucosa in women; however, its pathogenesis remains unclear. We have investigated the involvement of the endoplasmic reticulum (ER) in the induction of apoptosis by T. vaginalis and its molecular mechanisms in human cervical cancer SiHa cells. METHODS: Apoptosis, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), ER stress response and Bcl-2 family protein expression were evaluated using immunocytochemistry, flow cytometry, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide dye staining and western blotting. RESULTS: Trichomonas vaginalis induced mitochondrial ROS production, apoptosis, the ER stress response and mitochondrial dysfunction, such as MMP depolarization and an imbalance in Bcl-2 family proteins, in SiHa cells in a parasite burden- and infection time-dependent manner. Pretreatment with N-acetyl cysteine (ROS scavenger) or 4-phenylbutyric acid (4-PBA; ER stress inhibitor) significantly alleviated apoptosis, mitochondrial ROS production, mitochondrial dysfunction and ER stress response in a dose-dependent manner. In addition, T. vaginalis induced the phosphorylation of apoptosis signal regulating kinase 1 (ASK1) and c-Jun N-terminal kinases (JNK) in SiHa cells, whereas 4-PBA or SP600125 (JNK inhibitor) pretreatment significantly attenuated ASK1/JNK phosphorylation, mitochondrial dysfunction, apoptosis and ER stress response in SiHa cells, in a dose-dependent manner. Furthermore, T. vaginalis excretory/secretory products also induced mitochondrial ROS production, apoptosis and the ER stress response in SiHa cells, in a time-dependent manner. CONCLUSIONS: Trichomonas vaginalis induces apoptosis through mitochondrial ROS and ER stress responses, and also promotes ER stress-mediated mitochondrial apoptosis via the IRE1/ASK1/JNK/Bcl-2 family protein pathways in SiHa cells. These data suggest that T. vaginalis-induced apoptosis is affected by ROS and ER stress response via ER-mitochondria crosstalk.

Transmission Dynamics of Schistosoma haematobium among School-Aged Children: A Cohort Study on Prevalence, Reinfection and Incidence after Mass Drug Administration in the White Nile State of Sudan.

The reinfection rate of schistosomiasis after mass drug administration (MDA) has not been documented in Sudan. We aimed to explore the transmission dynamics of urogenital schistosomiasis after MDA, targeting school-aged children in the White Nile State of Sudan, assessing the prevalence, reinfection rate, and incidence. A single dose of praziquantel (40 mg/kg) was administered to 1951 students in five primary schools from January to February 2018 immediately after a baseline survey, and follow-up surveys were performed at 2 weeks and 6 months after treatment. We examined Schistosoma haematobium eggs by centrifugation methods. The overall reinfection rate at 6 months after treatment was 9.8% (95% confidence interval: 0.5-17.4%). By school, the reinfection rate was highest in the Al Hidaib school, whose prevalence was highest at baseline. The reinfection rate was significantly higher in high-infection areas than low-infection areas (p = 0.02). Of the prevalence at 6 months in high-infection areas, 41% of cases were due to reinfection. MDA interventions are decided upon and undertaken at the district level. A more targeted treatment strategy should be developed with a particular focus on tracking high-risk groups, even within a school or a community.

FAF1 downregulation by Toxoplasma gondii enables host IRF3 mobilization and promotes parasite growth.

Fas-associated factor 1 (FAF1) has gained a reputation as a member of the FAS death-inducing signalling complex. However, the role of FAF1 in the immunity response is not fully understood. Here, we report that, in the human retinal pigment epithelial (RPE) cell line ARPE-19 cells, FAF1 expression level was downregulated by Toxoplasma gondii infection, and PI3K/AKT inhibitors reversed T. gondii-induced FAF1 downregulation. In silico analysis for the FAF1 promoter sequence showed the presence of a FOXO response element (FRE), which is a conserved binding site for FOXO1 transcription factor. In accordance with the finding, FOXO1 overexpression potentiated, whereas FOXO1 depletion inhibited intracellular FAF1 expression level. We also found that FAF1 downregulation by T. gondii is correlated with enhanced IRF3 transcription activity. Inhibition of PI3K/AKT pathway with specific inhibitors had no effect on the level of T. gondii-induced IRF3 phosphorylation but blocked IRF3 nuclear import and ISGs transcription. These results suggest that T. gondii can downregulate host FAF1 in PI3K/AKT/FOXO1-dependent manner, and the event is essential for IRF3 nuclear translocation to active the transcription of ISGs and thereby T. gondii proliferation.

Population Dynamics of Intermediate-Host Snails in the White Nile River, Sudan: A Year-Round Observational Descriptive Study.

We aimed to explore the population dynamics of snail in 3 sites of the White Nile in Sudan. More specifically, we aimed to investigate the annual patterns of snail populations that act as intermediate hosts of schistosomes and monthly snail infection rates and ecological characteristics presumably related to snail populations. We collected snails for 1 year monthly at 3 different shore sites in the vicinity of El Shajara along the White Nile river in Khartoum State, Sudan. In addition, we measured air and water temperatures, water turbidities, vegetation coverages, and water depths and current speeds. Most of the collected snails were Biomphalaria pfeifferi and Bulinus truncatus. The population densities of snails and their infection rates varied across survey sites. The collected snails liberated S. mansoni and S. haematobium cercariae as well as Amphistome and Echinostome cercariae. Infected snails were found during March-June. The ecological characteristics found to be associated with the absence of snails population were: high turbidity, deep water, low vegetation coverage (near absence of vegetation), high water temperature, and high current speed. To our knowledge, this is the first longitudinal study of the snail population and ecological characteristics in the main basin of the White Nile river.

Silver nanoparticles induce apoptosis via NOX4-derived mitochondrial reactive oxygen species and endoplasmic reticulum stress in colorectal cancer cells.

Aim: To investigate the anticancer mechanisms of silver nanoparticles (AgNPs) in colorectal cancer. Methods: Anticancer effects of AgNPs were determined in colorectal cancer HCT116 cells and xenograft mice using cellular and molecular methods. Results: AgNPs induced mitochondrial reactive oxygen species production, mitochondrial dysfunction and endoplasmic reticulum (ER) stress responses through NOX4 and led to HCT116 cell apoptosis. Pretreatment with DPI or 4-PBA significantly inhibited mitochondrial reactive oxygen species production, apoptosis, ER stress response, NOX4 expression and mitochondrial dysfunction in AgNP-treated HCT116 cells. AgNPs also significantly suppressed HCT116 cell-based xenograft tumor growth in nude mice by inducing apoptosis and ER stress responses. Conclusion: AgNPs exert anticancer effects against colorectal cancer via ROS- and ER stress-related mitochondrial apoptosis pathways.

Expression profiles of NOD-like receptors and regulation of NLRP3 inflammasome activation in Toxoplasma gondii-infected human small intestinal epithelial cells.

BACKGROUND: Toxoplasma gondii is a parasite that primarily infects through the oral route. Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) play crucial roles in the immune responses generated during parasitic infection and also drive the inflammatory response against invading parasites. However, little is known about the regulation of NLRs and inflammasome activation in T. gondii-infected human small intestinal epithelial (FHs 74 Int) cells. METHODS: FHs 74 Int cells infected with T. gondii were subsequently evaluated for morphological changes, cytotoxicity, expression profiles of NLRs, inflammasome components, caspase-cleaved interleukins (ILs), and the mechanisms of NLRP3 and NLRP6 inflammasome activation. Immunocytochemistry, lactate dehydrogenase assay, reverse transcription polymerase chain reaction (RT-PCR), real-time quantitative RT-PCR, and western blotting techniques were utilized for analysis. RESULTS: Under normal and T. gondii-infected conditions, members of the NLRs, inflammasome components and caspase-cleaved ILs were expressed in the FHs Int 74 cells, except for NLRC3, NLRP5, and NLRP9. Among the NLRs, mRNA expression of NOD2, NLRP3, NLRP6, and NAIP1 was significantly increased in T. gondii-infected cells, whereas that of NLRP2, NLRP7, and CIITA mRNAs decreased significantly in a time-dependent manner. In addition, T. gondii infection induced NLRP3, NLRP6 and NLRC4 inflammasome activation and production of IL-1ß, IL-18, and IL-33 in FHs 74 Int cells. T. gondii-induced NLRP3 inflammasome activation was strongly associated with the phosphorylation of p38 MAPK; however, JNK1/2 had a weak effect. NLRP6 inflammasome activation was not related to the MAPK pathway in FHs 74 Int cells. CONCLUSIONS: This study highlighted the expression profiles of NLRs and unraveled the underlying mechanisms of NLRP3 inflammasome activation in T. gondii-infected FHs 74 Int cells. These findings may contribute to understanding of the mucosal and innate immune responses induced by the NLRs and inflammasomes during T. gondii infection in FHs 74 Int cells.

Parasitological Observation in Schoolchildren with Urogenital Schistosomiasis Following Treatment with Three Different Brands of Praziquantel.

This study compared the anthelminthic effects of three different brands of praziquantel being used in Sudan against Schistosoma haematobium (S. haematobium) infection. We enrolled 1,286 schoolchildren from six primary schools and examined their urine samples for eggs of S. haematobium at the baseline survey and follow-up two weeks after administering the medication. The schoolchildren were divided into three groups based on the three brands of praziquantel (different material production), with two school children for one brand. The overall baseline prevalence of S. haematobium infection was 15.5%. Two weeks after treatment with brands A, B, and C of praziquantel, cure rates were 87.1%, 82.4% and 83.8% respectively, and the egg-reduction rates were 69.0%, 81.0% and 70.6% respectively. There was no statistically significant difference in cure rates and egg-reduction rates between the three brands. We conclude that the three different commercial brands of praziquantel used in Sudan have similar anthelminthic effects on S. haematobium.