Forsythia velutina Nakai extract: A promising therapeutic option for atopic dermatitis through multiple cell type modulation.

BACKGROUND: Atopic dermatitis (AD) is a complex condition characterized by impaired epithelial barriers and dysregulated immune cells. In this study, we demonstrated Forsythia velutina Nakai extract (FVE) simultaneously inhibits basophils, macrophages, keratinocytes, and T cells that are closely interrelated in AD development. METHODS: We analyzed the effect of FVE on nitric oxide and reactive oxygen species (ROS) production in macrophages, basophil degranulation, T cell activation, and tight junctions in damaged keratinocytes. Expression of cell-type-specific inflammatory mediators was analyzed, and the underlying signaling pathways for anti-inflammatory effects of FVE were investigated. The anti-inflammatory effects of FVE were validated using a DNCB-induced mouse model of AD. Anti-inflammatory activity of compounds isolated from FVE was validated in each immune cell type. RESULTS: FVE downregulated the expression of inflammatory mediators and ROS production in macrophages through TLR4 and NRF2 pathways modulation. It significantly reduced basophil degranulation and expression of type 2 (T2) and pro-inflammatory cytokines by perturbing FcεRI signaling. Forsythia velutina Nakai extract also robustly inhibited the expression of T2 cytokines in activated T cells. Furthermore, FVE upregulated the expression of tight junction molecules in damaged keratinocytes and downregulated leukocyte attractants, as well as IL-33, an inducer of T2 inflammation. In the AD mouse model, FVE showed superior improvement in inflammatory cell infiltration and skin structure integrity compared to dexamethasone. Dimatairesinol, a lignan dimer, was identified as the most potent anti-inflammatory FVE compound. CONCLUSION: Forsythia velutina Nakai extract and its constituent compounds demonstrate promising efficacy as a therapeutic option for prolonged AD treatment by independently inhibiting various cell types associated with AD and disrupting the deleterious link between them.

Gut microbiota differences induced by Toxoplasma gondii seropositivity in stray cats in South Korea.

T. gondii is a highly prevalent parasite worldwide, with cats serving as its final host. However, few studies have investigated the impact of T. gondii infection on cat gut microbiota. Therefore, this study examined the influence of T. gondii infection on the gut microbiota of stray cats and identified potential pathogens in their feces. This study examined T. gondii infection through blood of stray cats and the influence of microbiota in their feces using 16S rRNA gene amplicon sequencing. The results revealed significant differences in gut microbiota composition and diversity between the T. gondii seropositive and seronegative groups. Seropositive samples displayed a lower number of operational taxonomic units and reduced Shannon index than the seronegative samples. The seropositive and seronegative groups exhibited enrichment of taxa, including Escherichia and Enterobacteriaceae and Collinsella, Bifidobacterium, and Roseburia, respectively. Furthermore, potential pathogen species, including Campylobacter, Escherichia, and Streptococcus, were identified in the fecal samples. These findings suggest that T. gondii infection significantly impacts gut microbiota composition and diversity in stray cats. Additionally, an increased potential pathogen load, represented by Escherichia spp., was observed. These results underscore the importance of monitoring the prevalence of zoonotic pathogens in stray cats, as they can serve as reservoirs for zoonotic diseases.

Lithium chloride inhibits the migration and invasion of osteosarcoma cells by blocking nuclear translocation of phospho-Erk.

Lithium chloride (LiCl) is an important mood-stabilizing therapeutic agent for bipolar disorders, which has also been shown to inhibit cancer cell metastasis. Investigations of LiCl-induced signaling have focused mainly on extracellular signal regulated kinase 1/2 (ERK1/2) and glycogen synthase kinase 3 (GSK-3). However, little is known about the differences in cellular activities resulting from specific signaling via each of these pathways. In this study, we investigated the difference in responses between the Wnt/ß-catenin and ERK pathways by LiCl or epidermal growth factor (EGF) treatment of osteosarcoma cells. In particular, we analyzed the mechanisms responsible for differences in cell mobility and cell proliferation when pERK or ß-catenin is activated. In osteosarcoma cells treated with LiCl or EGF, active ß-catenin and p-ERK protein levels were significantly increased compared to those in the control group. However, in wound healing and transwell invasion assays, U2OS and SaOS2 cell migration was significantly reduced by LiCl treatment but increased by EGF treatment. In addition, the proliferation of U2OS cells was reduced by LiCl treatment but increased by EGF treatment. Using immunofluorescence microscopy, we observed nuclear accumulation of phosphorylated ERK (pERK) with EGF treatment, but pERK was restricted to the perinuclear area with LiCl treatment. These results were confirmed using immunoblot assays after subcellular fractionation. Together, these data suggest that LiCl interferes with the translocation of pERK from the cytoplasm to the nucleus.

Microbiome and mycobiome interaction in house dust mites and impact on airway cells.

BACKGROUND: Major allergen sources Dermatophagoides farinae, Dermatophagoides pteronyssinus and Tyrophagus putrescentiae have been reported to have distinct microbiomes. The purpose of this study was to investigate the effect of each mite on airway epithelial cells as a model of airway allergic disease. METHODS: Transcriptomic analysis (RNA-seq) of an airway epithelial cell line (BEAS-2B) was performed to compare gene expression patterns after treatment with extracts of three mite species (D. farinae, D. pteronyssinus and T. putrescentiae). In addition, mycobiome deep sequencing of mites was employed to identify fungal species that interact with the microbiomes of the mites. RESULTS: Immune responses to bacteria were enriched only in the D. farinae-treated group as this species harboured larger numbers of bacteria than the other mites, and the high level of LPS in D. farinae caused proinflammatory cytokine production in airway epithelial cells. In addition, antibiotic metabolism pathways were enriched in D. pteronyssinus-treated cells but not in D. farinae -treated cells. Subsequent experiments revealed that D. pteronyssinus had a high fungal load that inhibited bacterial survival in this mite species. CONCLUSION: The large amount of bacteria in D. farinae causes airway epithelial cells to produce more allergy-related cytokines than D. pteronyssinus, since fungi present in D. pteronyssinus suppress the abundance of mite-associated bacteria.

Association between Sociodemographic Factors and Diarrhea in Children Under 5 Years in Rwanda.

Diarrheal disease is the second leading cause of mortality and morbidity in children under 5 years old worldwide, and is the most common cause of malnutrition in sub-Saharan Africa. In Rwanda, diarrhea is the third leading cause of death in children under 5 years old. This study examined the association between sociodemographic factors and diarrhea in children under 5 years using the data of 7,474 households in the 2014-2015 Rwanda Demographic and Health Survey. Overall prevalence of diarrhea in this study was 12.7% in children. An increased risk for diarrhea was found for children aged 12-23 months (odds ratio (OR)=4.514), those with a low economic status (OR=1.64), those from the Western province (OR=1.439), those with poorly-educated mothers (OR=5.163), and those with families engaged in agricultural activities (OR=1.624). In conclusion, sociodemographic factors significantly affect the risk of developing diarrhea in children under 5 years in Rwanda. Designing and implementing health education promoting awareness of early interventions and rotavirus vaccination are essential to reduce diarrheal diseases for the Rwandan community.

Microbiome of Haemaphysalis longicornis Tick in Korea.

Ticks can transmit pathogenic bacteria, protozoa, and viruses to humans and animals. In this study, we investigated the microbiomes of Haemaphysalis longicornis according to sex and life stages. The Shannon index was significantly higher for nymphs than adult ticks. Principal coordinates analysis showed that the microbiome composition of female adult and male adult ticks were different. Notably, Coxiella-like bacterium (AB001519), known as a tick symbiont, was found in all nymphs and female adult ticks, but only one out of 4 male adult ticks had Coxiella-like bacterium (AB001519). In addition, Rickettsia rickettsii, Coxiella burnetii, and Anaplasma bovis were detected in this study.

Molecular Detection of Toxoplasma Gondii in Haemaphysalis Ticks in Korea.

Toxoplasma gondii are intracellular protozoa that can cause neurological disease or death in fetuses and even in immunocompromised human adults. Ticks are recognized as vectors of many microorganisms including viruses, bacteria, and protozoa. Recent studies detected T. gondii in various tick species in many countries. In this study, we performed PCR detection of the T. gondii B1 gene from Haemaphysalis ticks collected from vegetation in 4 localities, Wonju, Gunsan, Miryang, and Yangsan, in Korea. We analyzed DNA from 314 ticks (268 Haemaphysalis longicornis and 46 Haemaphysalis flava) and the B1 gene of T. gondii was detected in 13 of these. The detection of T. gondii in ticks differed significantly by region (P=0.021). T. gondii was detected in the following percentages of collected ticks: 3.7% (7 of 189) in Gunsan, 10% (5 of 50) in Wonju, 16.7% (1 of 6) in Yangsan, and 0% (0 of 69) in Miryang. The detection of T. gondii in ticks was not associated with tick species or development stage. This is the first report of T. gondii detection in ticks in Korea. Our results provide important information necessary to understand toxoplasmosis transmission.

Comparative Microbiome Analysis of Three Species of Laboratory-Reared Periplaneta Cockroaches.

Cockroaches inhabit various habitats, which will influence their microbiome. Although the microbiome can be influenced by the diet and environmental factors, it can also differ between species. Therefore, we conducted 16S rDNAtargeted high-throughput sequencing to evaluate the overall bacterial composition of the microbiomes of 3 cockroach species, Periplaneta americana, P. japonica, and P. fuliginosa, raised in laboratory for several generations under the same conditions. The experiments were conducted using male adult cockroaches. The number of operational taxonomic units (OTUs) was not significantly different among the 3 species. With regard to the Shannon and Pielou indexes, higher microbiome values were noted in P. americana than in P. japonica and P. fuliginosa. Microbiome composition was also evaluated, with endosymbionts accounting for over half of all OTUs in P. japonica and P. fuliginosa. Beta diversity analysis further showed that P. japonica and P. fuliginosa had similar microbiome composition, which differed from that of P. americana. However, we also identified that P. japonica and P. fuliginosa host distinct OTUs. Thus, although microbiome compositions may vary based on multiple conditions, it is possible to identify distinct microbiome compositions among different Periplaneta cockroach species, even when the individuals are reared under the same conditions.

Effectiveness of Mass Drug Administration on Neglected Tropical Diseases in Schoolchildren in Zanzibar, Tanzania.

Soil-transmitted helminths and Schistosoma haematobium affect more than 3 billion people globally and mainly occur in sub-Saharan Africa. The present study assessed the overall infection status of a 1716-student cohort of school-children in Zanzibar and applied mass drug administration (MDA) to the cohort from 2007 to 2009. Schools in Pemba, Zanzibar, had a much higher prevalence of soil-transmitted helminth infections than those in Unguja, and the Chaani, Ghana, and Machui schools of Unguja exhibited high S. haematobium infection rates. The MDA program only partially controlled parasite infections, owing to high rates of re-infection. The infection rate of S. haematobium across all 10 schools, for example, was only reduced by 1.8%, and even this change not significant, even though the S. haematobiuminfection rates of the Chaani and Mzambarauni schools were significantly reduced from 64.4 and 23.4%, respectively, at the first screening, to 7.3 and 2.3% at the last screening. The overall infection rate of Ascaris lumbricoides was reduced from 36.0% at the first screening to 22.6% at the last screening. However, the infection rates for both Trichuris trichiuraand hookworm were generally unaffected by MDA. In the future, parasite control programs should involve strategically designed MDA schedules and holistic intervention (e.g., sanitation improvement, hygiene behavior changes, and control of intermediated hosts).

Chinese liver fluke Clonorchis sinensis infection changes the gut microbiome and increases probiotic Lactobacillus in mice.

Chinese liver fluke Clonorchis sinensis changes the host's immune system. Recently, it has been reported that helminths including C. sinensis can ameliorate immune-related diseases such as allergy. In addition, recent studies showed that helminth infection can alleviate immune-mediated disorders by altering the gut microbiome. However, changes in the gut microbiome due to C. sinensis have not been reported yet. In this study, changes in the gut microbiome of C57BL/6 mice infected with C. sinensis metacercariae were evaluated over time. Stool was analyzed by 16S rRNA amplicon analysis using high-throughput sequencing technology. There was no apparent difference in species richness and diversity between the infected and control groups. However, the composition of the microbiome was different between the infected and control groups at 20 days and 30 days post-infection, and the difference disappeared at 50 days post-infection. In particular, this microbiome alteration was associated with a change in the relative abundance of genus Lactobacillus and the probiotic Lactobacillus species that are known to have an immune-modulation role in immune-mediated diseases.

Social networks as drivers of syphilis and HIV infection among young men who have sex with men.

OBJECTIVES: Syphilis and HIV epidemics overlap, yet little is known about combined network and behavioural factors that drive syphilis-HIV coinfection. Our study objective was to assess network contexts and sexual behaviours associated with syphilis-HIV co-infection and monoinfection among a particularly vulnerable subgroup: young Black men who have sex with men (YBMSM). To achieve this objective, we examined factors associated with coinfection by each subgroup as classified by syphilis-HIV infection status: (A) HIV monoinfected, (B) syphilis monoinfected and (C) neither syphilis infected nor HIV infected. In addition, we further identified the factors that are associated with HIV infection or syphilis monoinfection. METHODS: Data were collected from a sample of 365 YBMSM, aged 16-29 years, recruited through respondent-driven sampling between 2014 and 2016, in two cities with large HIV epidemics: Houston, TX, and Chicago, IL. We conducted a series of multinomial logistic regression models to predict coinfection, HIV monoinfection and syphilis monoinfection as a function of network and sexual behavioural factors. RESULTS: Coinfection was associated with having network members who are coinfected or HIV infected within one's social network. Syphilis monoinfection was associated with a higher number of social venues attended, and HIV monoinfection was associated with having more condomless top partners. CONCLUSION: Public health interventions that address the diagnosis and treatment of syphilis infection and ensure that those with syphilis are being tested for HIV may be promising in limiting the synergy of syphilis-HIV infections in onward transmission. Advancing HIV and syphilis prevention efforts in high-prevalence networks may allow prioritisation of limited resources.

Recombinant adenylate kinase 3 from liver fluke Clonorchis sinensis for histochemical analysis and serodiagnosis of clonorchiasis.

Due to the lack of an effective prophylactic intervention and diagnosis, human liver fluke Clonorchis sinensis continues to afflict a large human population, causing a chronic inflammatory bile duct disease. With an aim to identify target antigens for sensitive serodiagnosis, adenylate kinase 3 of C. sinensis (CsAK3) was successfully expressed in soluble form in Escherichia coli by fusion to an RNA-interacting domain derived from human Lys-tRNA synthetase and purified by Ni2+-affinity chromatography. Anti-CsAK3 serum was raised by immunization of mice, and Western blotting confirmed that CsAK3 was expressed in adult-stage C. sinensis. Histochemical analysis showed that CsAK3 was localized to the subtegumental tissue of C. sinensis and was excreted into the bile duct of the host. When tested against sera from various parasite-infected patients by enzyme-linked immunosorbent assay, the recombinant CsAK3 elicited a specific response to C. sinensis-infected sera. The results suggest that CsAK3, either alone or in combination with other antigens, could be used for improving the clinical diagnosis of clonorchiasis.

Intestinal fluke Metagonimus yokogawai infection increases probiotic Lactobacillus in mouse cecum.

Helminth infection can alleviate immune-mediated disorders such as allergies and autoimmune diseases, by altering the gut microbiome. However, changes in gut microbiome due to intestinal trematodes remain unelucidated. Here, we evaluated the changes in the gut microbiome of ICR mice infected with Metagonimus yokogawai, a hypo-virulent intestinal trematode. Four weeks after infection, mouse cecal content was analyzed by 16S rRNA amplicon analysis. Although there was no apparent difference in species richness and diversity, the microbiome composition was different in the infected and control groups. Furthermore, several Lactobacillus species with known immunomodulatory role in immune-mediated diseases were increased in the infected group.

Prevalence of Tick-Borne Pathogens from Ticks Collected from Cattle and Wild Animals in Tanzania in 2012.

This study was aimed to disclose the prevalence rate of tick-borne pathogens from ticks collected from cattle and wild animals in Tanzania in 2012. Ticks were collected from slaughtered cattle and dead wild animals from November 5 to December 23, 2012 and identified. PCR for detecting Anaplasmataceae, Piroplamidae, Rickettsiaceae, Borrelia spp., and Coxiella spp. were done. Among those tested, Rickettsiaceae, Piroplasmidae, and Anaplasmataceae, were detected in ticks from the 2 regions. Rickettsiaceae represented the major tick-borne pathogens of the 2 regions. Ticks from animals in Maswa were associated with a higher pathogen detection rate compared to that in ticks from Iringa. In addition, a higher pathogen detection rate was observed in ticks infesting cattle than in ticks infesting wild animals. All examined ticks of the genus Amblyomma were infected with diverse pathogens. Ticks of the genera Rhipicephalus and Hyalomma were infected with 1 or 2 pathogens. Collectively, this study provides important information regarding differences in pathogen status among various regions, hosts, and tick species in Tanzania. Results in this study will affect the programs to prevent tick-borne diseases (TBD) of humans and livestock in Tanzania.

Network Centrality and Geographical Concentration of Social and Service Venues that Serve Young Men Who Have Sex with Men.

This study examines network centrality of inter-venue networks formed by collaboration, competition, and sponsorship relationships among venues that serve young men who have sex with men (MSM) aged 16-29 years in relation to their geographical concentrations in Chicago, Illinois, and Houston, Texas. Our data on the physical venues comprised 116 venues in Chicago and 102 venues in Houston. We examined the relationship between the network centrality of different relations and the geographical intensity among these venues, and considered neighborhood-level socioeconomic determinants of health. The results indicate that young MSM-serving social and service venues found in close physical proximity to one another tend to have large centrality indegree values based on competition in both cities, and based on collaboration only in Chicago. No evidence, however, was found that occupying a central position in the sponsorship networks was related to geographic concentration. Combined, these results suggest that HIV prevention interventions should consider the organizing force for competition. Such a strategy could result in better services. However there may still be potential for overlap and redundancy in services at the expense of under-served regions where proven interventions could have the greatest impact.

Multiplex crack smoking and sexual networks: associations between network members' incarceration and HIV risks among high-risk MSM.

This study examined HIV risks in the multiplex crack-smoking and sexual networks of incarcerated drug-using men who have sex with men (MSM) and their associates. We estimated the associations between the network members' incarceration, self-reported HIV infection, and trading sex for money. Our analytic sample consisted of 508 crack-smoking or sexual partnerships of 273 high-risk MSM. Network members were specified by (1) crack smoking and sexual behavior or (2) crack smoking only. Longer incarceration of the crack-smoking and sexual network members was associated with self-reported HIV infection (AOR = 1.61, p < 0.05), which extended up to one's partners' partners' partners (AOR = 1.63, p < 0.05). Similar results were found for trading sex (AOR = 2.77, p < 0.05). The findings of the study call for the development of a system-level HIV intervention among former incarcerated MSM and their associates.

Semimembranosus Release for Medial Soft Tissue Balancing Does Not Weaken Knee Flexion Strength in Patients Undergoing Varus Total Knee Arthroplasty.

BACKGROUND: The sequential medial release technique including semimembranosus (semiM) release is effective and safe during varus total knee arthroplasty (TKA). However, there are concerns about weakening of knee flexion strength after semiM release. We determined whether semiM release to balance the medial soft tissue decreased knee flexion strength after TKA. METHODS: Fifty-nine consecutive varus knees undergoing TKA were prospectively enrolled. A 3-step sequential release protocol which consisted of release of (1) the deep medial collateral ligament (dMCL), (2) the semiM, and (3) the superficial medial collateral ligament based on medial tightness. Gap balancing was obtained after dMCL release in 31 knees. However, 28 knees required semiM release or more after dMCL release. Isometric muscle strength of the knee was compared 6 months postoperatively between the semiM release and semiM nonrelease groups. Knee stability and clinical outcomes were also compared. RESULTS: No differences in knee flexor or extensor peak torque were observed between the groups 6 months postoperatively (P = .322 and P = .383, respectively). No group difference was observed in medial joint opening angle on valgus stress radiographs (P = .327). No differences in the Knee Society or Western Ontario and McMaster Universities Osteoarthritis Index scores were detected between the groups (P = .840 and P = .682, respectively). CONCLUSION: These results demonstrate that semiM release as a sequential step to balance medial soft tissue in varus knees did not affect knee flexion strength after TKA.

Clinical and radiological outcomes of unstable proximal humeral fractures treated with a locking plate and fibular strut allograft.

PURPOSE: To evaluate the clinical and radiological outcomes of unstable proximal humeral fractures (PHFs) treated with a locking plate and fibular strut allograft. METHODS: This study included 36 patients [7 men, 29 women; mean age, 68 years (range, 22-94 years)] with unstable PHFs with medial column disruption. All patients were treated with open reduction and internal fixation using a locking plate and fibular strut allograft. Post-operative assessment included clinical outcomes, shoulder range of motion, radiographic examination, and any complications. Post-operative radiological assessment including the humerus neck-shaft angle (NSA) and the humeral head height was performed. RESULTS: At the mean two year follow-up visit, the mean American Shoulder and Elbow Society (ASES) and University of California, Los Angeles (UCLA) scores were 77 and 28, respectively. According to the UCLA rating scale, the result was excellent in six, good in 20, fair in six, and poor in four cases. According to the Paavolainen method, 31 patients had good results with an NSA of 130 ± 10°; three patients showed fair results with an NSA of 100-120°, and two patients experienced a poor result with an NSA of <100°. When calculating the humeral head height, the mean loss of reduction was measured as 1.6 mm (from 10.8 or 9.2 mm). Varus collapse and avascular necrosis of the humeral head was noted in two patients for each condition. CONCLUSIONS: For unstable proximal humerus fractures, particularly in elderly patients with severe osteoporosis or in younger patients with a four-part fracture, locking plate fixation with a fibular strut allograft provided rigid medial support and showed satisfactory clinical and radiological outcomes.

Learning Curve Analysis and Surgical Outcomes of Single-port Laparoscopic Myomectomy.

STUDY OBJECTIVE: To identify learning curves for single-port laparoscopic myomectomy (SPLM) and evaluate surgical outcomes according to the sequence of operation. DESIGN: A retrospective study. SETTING: A university-based hospital (Canadian Task Force classification II-2). PATIENTS: The medical records from 205 patients who had undergone SPLM from October 2009 to May 2013 were reviewed. Because the myomectomy time was significantly affected by the size and number of myomas removed by SPLM, cases in which 2 or more of the myomas removed were >7 cm in diameter were excluded. Furthermore, cases involving additional operations performed simultaneously (e.g., ovarian or hysteroscopic surgery) were also excluded. A total of 161 cases of SPLM were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We assessed the SPLM learning curve via a graph based on operation time versus sequence of cases. Patients were chronologically arranged according to their surgery dates and were then placed into 1 of 4 groups according to their operation sequence. SPLM was completed successfully in 160 of 161 cases (99.4%). One case was converted to multiport surgery. Basal characteristics of the patients between the 4 groups did not differ. The median operation times for the 4 groups were 112.0, 92.8, 83.7, and 90.0 minutes, respectively. Operation time decreased significantly in the second, third, and fourth groups compared with that in the first group (p < .001). Proficiency, which is the point at which the slope of the learning curve became less steep, was evident after about 45 operations. CONCLUSION: Results from the current study suggested that proficiency for SPLM was achieved after about 45 operations. Additionally, operation time decreased with experience without an increase in complication rate.