Effects Of Infectious Diseases Research Articles

The Effects of Infectious Diseases on the Consequences of Interspecific Competition in Grassland Communities

As infectious diseases have a severe impact on the individual survival and competitive ability of host species in grassland communities, competition between relevant species may have different consequences, potentially influencing the species composition of grassland communities and the functioning of grassland ecosystems. Understanding the impact of infectious diseases on competition is thus crucial for the health management of grassland ecosystems. How do infectious diseases affect the competitive coexistence of grassland plant species? In this study, by drawing on Tilman’s multispecies competition model and incorporating the spread characteristics of grassland plant diseases, we built three spatial competition models of two grass species subject to infectious diseases, and we analyzed the invasion conditions of infectious diseases and how they impact the population dynamics and competitive consequences of the species. Our model revealed the following: (1) Diseases with high transmission rates and low virulence are more likely to invade populations, while the presence of non-host species is detrimental to disease invasion. (2) Disease promotes the coexistence of competing species, breaking down the original competition–compromise trade-off mechanism for species coexistence and greatly expanding the range of parameters within which the two species can coexist. (3) Pathogen infections indirectly weaken the suppression of inferior species by dominant species, which is similar to the cascade effect seen in trophic interactions. Our findings highlight the importance of disease in species coexistence and grassland biodiversity maintenance.

The effect of infectious diseases on lung transplantation in Japan.

Lung transplantation in Japan is an increasingly accessible treatment option for end-stage lung disease; however, the lack of donor organs is a persisting challenge. Five- and 10-year survival rates of lung transplant recipients in Japan are comparable, if not superior, to international standards. The outcomes of lung transplantation in Japan are likely affected by multiple factors. Infectious disease complications are a significant burden to transplant recipients and account for approximately 30% of recipient mortality in Japan, presenting a major challenge in peri-transplant management. Herein, we explore the current status of infectious disease epidemiology, available evidence surrounding infectious diseases in lung transplantation, and potentially influential factors pertinent to lung transplantation outcomes in Japan. Although infection remains the major cause of morbidity and mortality associated with lung transplantation in Japan, there is limited data and evidence. Despite some uncertainties, publicly available data suggests a low rate of antimicrobial resistance in Gram-negative bacteria and a distinct set of endemic pathogens that recipients may encounter. As a countermeasure against the burden of infectious diseases, 8 out of 10 transplant centers in Japan have a dedicated infectious diseases department. Despite these efforts, specific surveillance, prevention, and management are indispensable to improving post-transplantation infectious disease management. We accordingly lay out potential areas for improving infectious disease-related outcomes among lung transplant recipients in Japan.

Novel insights into IL-37: an anti-inflammatory cytokine with emerging roles in anti-cancer process.

Interleukin-37 (IL-37) is a newly discovered member of IL-1 family. The cytokine was proved to have extensive protective effects in infectious diseases, allergic diseases, metabolic diseases, autoimmune diseases and tumors since its discovery. IL-37 was mainly produced by immune and some non-immune cells in response to inflammatory stimulus. The IL-37 precursors can convert into the mature forms after caspase-1 cleavage and activation intracellularly, and then bind to Smad-3 and transfer to the nucleus to inhibit the production and functions of proinflammatory cytokines; extracellularly, IL-37 binds to cell surface receptors to form IL-37/IL-18Rα/IL-1R8 complex to exert immunosuppressive function via inhibiting/activating multiple signal pathways. In addition, IL-37 can attenuate the pro-inflammatory effect of IL-18 through directly or forming an IL-37/IL-18BP/IL-18Rβ complex. Therefore, IL-37 has the ability to suppress innate and acquired immunity of the host, and effectively control inflammatory stimulation, which was considered as a new hallmark of cancer. Specifically, it is concluded that IL-37 can inhibit the growth and migration of tumor cells, prohibit angiogenesis and mediate the immunoregulation in tumor microenvironment, so as to exert effective anti-tumor effects. Importantly, latest studies also showed that IL-37 may be a novel therapeutic target for cancer monitoring. In this review, we summarize the immunoregulation roles and mechanisms of IL-37 in anti-tumor process, and discuss its progress so far and potential as tumor immunotherapy.

Drug repositioning via host-pathogen protein-protein interactions for the treatment of cervical cancer.

Integrating interaction data with biological knowledge can be a critical approach for drug development or drug repurposing. In this context, host-pathogen-protein-protein interaction (HP-PPI) networks are useful instrument to uncover the phenomena underlying therapeutic effects in infectious diseases, including cervical cancer, which is almost exclusively due to human papillomavirus (HPV) infections. Cervical cancer is one of the second leading causes of death, and HPV16 and HPV18 are the most common subtypes worldwide. Given the limitations of traditionally used virus-directed drug therapies for infectious diseases and, at the same time, recent cancer statistics for cervical cancer cases, the need for innovative treatments becomes clear. Accordingly, in this study, we emphasize the potential of host proteins as drug targets and identify promising host protein candidates for cervical cancer by considering potential differences between HPV subtypes (i.e., HPV16 and HPV18) within a novel bioinformatics framework that we have developed. Subsequently, subtype-specific HP-PPI networks were constructed to obtain host proteins. Using this framework, we next selected biologically significant host proteins. Using these prominent host proteins, we performed drug repurposing analysis. Finally, by following our framework we identify the most promising host-oriented drug candidates for cervical cancer. As a result of this framework, we discovered both previously associated and novel drug candidates, including interferon alfacon-1, pimecrolimus, and hyaluronan specifically for HPV16 and HPV18 subtypes, respectively. Consequently, with this study, we have provided valuable data for further experimental and clinical efforts and presented a novel bioinformatics framework that can be applied to any infectious disease.

Advancing global health and the sustainable development goals through transdisciplinary research and equitable publication practices

Advancing global health and the sustainable development goals through transdisciplinary research and equitable publication practices

How does fear of COVID-19 affect the mental well-being of waiters in Turkey

BACKGROUND: Empirical findings are needed to determine how the fear of COVID-19 might change in the context of different individuals. OBJECTIVE: This study aims to determine the moderating role of fatalism and psychological resilience on the effect of fear of COVID-19 on general mental health. METHODS: This study makes use of qualitative research methods that involved collecting data from 355 full-time waiters via questionnaires on online platforms. RESULT: The collected data suggests that the fear of COVID-19 has a significant negative impact on mental well-being. Morever, the data gathered for this study also indicates that the fear of COVID-19 infection differs significantly according to the fatalistic belief and psychological resilience levels of the waiters. CONCLUSIONS: Findings of this study indicate that the psychological effects of infectious diseases on individuals are not universal, but rather depend on the personal characteristics of individuals. It is hoped that the results of this study will contribute to the reduction of negative effects associated with the general anxiety of pandemic that individuals experience.

Immunomodulatory effects of pharmaceutical opioids and antipyretic analgesics: Mechanisms and relevance to infection.

Understanding how pharmaceutical opioids and antipyretic analgesics interact with the immune system potentially has major clinical implications for management of patients with infectious diseases and surgical and critical care patients. An electronic search was carried out on MEDLINE, EMBASE, PsycINFO, CENTRAL and the Cochrane library to identify reports describing the immunomodulatory effects of opioid analgesics and antipyretic analgesics, and their effects in infectious diseases. In adaptive immunity, nonsteroidal anti-inflammatory drugs have divergent effects: augmenting cell-mediated immunity but inhibiting humoral immunity. Nonsteroidal anti-inflammatory drugs have demonstrated a beneficial role in Mycobacterium tuberculosis infection and histoplasmosis in animals, and may be plausible adjuvants to antimicrobial agents in these diseases. There is a need to evaluate these findings rigorously in human clinical trials. There is preliminary evidence demonstrating antiviral effects of indomethacin in SARS CoV-2 in vitro; however, uncertainty regarding its clinical benefit in humans needs to be resolved in large clinical trials. Certain opioid analgesics are associated with immunosuppressive effects, with a developing understanding that fentanyl, morphine, methadone and buprenorphine suppress innate immunity, whilst having diverse effects on adaptive immunity. Morphine suppresses key cells of the innate immunity and is associated with greater risk of infection in the postsurgical setting. Efforts are needed to achieve adequate analgesia whilst avoiding suppression of the innate immunity in the immediate postoperative period caused by certain opioids, particularly in cancer surgery.

Empirical Evidence on the Impact of Infectious Diseases on Health-Outcome in Nigeria

Purpose: This research is an empirical investigation on the rate in which infectious diseases have impacted on health outcome in Nigeria. Over the years, infectious diseases such as HIV/AIDS, Tuberculosis and others have been rampaging the health outcome of the people mostly those in Africa and in Nigeria to be precise. Many people have lost their precious life because of these infectious diseases and many are still in anticipation of losing their lives too. Efforts by the Nigeria government to curtail the prevalence of infectious diseases seems abortive. This paper is to find out the level in which infectious diseases have been affecting health outcome of the people in Nigeria and proffer a solution to the menace. Design/Methodology/Approach: This paper is an empirical research. The methodology used is the Auto Regressive Distributed Lag (ARDL) model which helps to find out the rate of impacts and effects of infectious diseases on health outcome in Nigeria. Being an empirical study, secondary annual data (1985 – 2018) were used and their sources are reliable. Findings: The result from the findings shows that infectious diseases have negative impacts on health outcome in Nigeria over the years of study. However, HIV/AIDS was significant at 10% over those years, while Tuberculosis showed no significance impact on health outcome. Originality/Value: This study approached infectious diseases and health outcome in Nigeria. It will help to foster good economic policies to curb the prevalence of infectious diseases and boast health outcome in Nigeria knowing that most of the efforts the government of Nigeria abducted previously seem abortive. The conclusion part of this study is a good policy implementation ideas and strategic plans to eradicate the menace.

Paradox of trimethylamine-N-oxide, the impact of malnutrition on microbiota-derived metabolites and septic patients

BackgroundTrimethylamine N-oxide (TMAO) is a microbiota-derived metabolite, which is linked to vascular inflammation and atherosclerosis in cardiovascular (CV) diseases. But its effect in infectious diseases remains unclear. We conducted a single-center prospective study to investigate association of TMAO with in-hospital mortality in septic patients admitted to an intensive care unit (ICU).MethodsTotally 95 septic, mechanically ventilated patients were enrolled. Blood samples were obtained within 24 h after ICU admission, and plasma TMAO concentrations were determined. Septic patients were grouped into tertiles according to TMAO concentration. The primary outcome was in-hospital death, which further classified as CV and non-CV death. Besides, we also compared the TMAO concentrations of septic patients with 129 non-septic patients who were admitted for elective coronary angiography (CAG).ResultsSeptic patients had significantly lower plasma TMAO levels than did subjects admitted for CAG (1.0 vs. 3.0 μmol/L, p < 0.001). Septic patients in the lowest TMAO tertile (< 0.4 μmol/L) had poorer nutrition status and were given longer antibiotic courses before ICU admission. Circulating TMAO levels correlated positively with daily energy intake, the albumin and prealbumin concentration. Compared with those in the highest TMAO tertile, septic patients in the lowest TMAO tertile were at greater risk of non-CV death (hazard ratio 2.51, 95% confidence interval 1.21–5.24, p = 0.014). However, TMAO concentration was no longer an independent predictor for non-CV death after adjustment for disease severity and nutritional status.ConclusionPlasma TMAO concentration was inversely associated with non-CV death among extremely ill septic patients, which could be characterized as TMAO paradox. For septic patients, the impact of malnutrition reflected by circulating TMAO levels was greater than its pro-inflammatory nature.

Sympatric threatened Iberian leuciscids exhibit differences in Aeromonas diversity and skin lesions' prevalence.

Assessments regarding health aspects of Iberian leuciscids are limited. There is currently an information gap regarding effects of infectious diseases on these populations and their role as a possible conservation threat. Moreover, differences in susceptibility to particular agents, such as Aeromonas spp., by different species/populations is not clear. To understand potential differences in Aeromonas diversity and load, as well as in the prevalence and proportion of skin lesions, in fishes exposed to similar environmental conditions, an observational study was implemented. Using a set of 12 individuals belonging to two sympatric Iberian leuciscid species (Squalius pyrenaicus and Iberochondrostoma lusitanicum), the skin lesion score in each individual was analyzed. Furthermore, a bacterial collection of Aeromonas spp. isolated from each individual was created and isolates' load was quantified by plate counting, identified at species level using a multiplex-PCR assay and virulence profiles established using classical phenotypic methods. The similarity relationships of the isolates were evaluated using a RAPD analysis. The skin lesion score was significantly higher in S. pyrenaicus, while the Aeromonas spp. load did not differ between species. When analyzing Aeromonas species diversity between fishes, different patterns were observed. A predominance of A. hydrophila was detected in S. pyrenaicus individuals, while I. lusitanicum individuals displayed a more diverse structure. Similarly, the virulence index of isolates from S. pyrenaicus was higher, mostly due to the isolated Aeromonas species. Genomic typing clustered the isolates mainly by fish species and skin lesion score. Specific Aeromonas clusters were associated with higher virulence indexes. Current results suggest potential differences in susceptibility to Aeromonas spp. at the fish species/individual level, and constitute important knowledge for proper wildlife management through the signalization of at-risk fish populations and hierarchization of conservation measures.

Threshold Effects of Infectious Disease Outbreaks on Livestock Prices: Cases of African Swine Fever and Avian Influenza in South Korea

In this paper we demonstrate the threshold effects of infectious diseases on livestock prices. Daily retail prices of pork and chicken were used as structured data; news and SNS mentions of African Swine Fever (ASF) and Avian Influenza (AI) were used as unstructured data. Models were tested for the threshold effects of disease-related news and SNS frequencies, specifically those related to ASF and AI, on the retail prices of pork and chicken, respectively. The effects were found to exist, and the values of ASF-related news on pork prices were estimated to be −9 and 8, indicating that the threshold autoregressive (TAR) model can be divided into three regimes. The coefficients of the ASF-related SNS frequencies on pork prices were 1.1666, 0.2663 and −0.1035 for regimes 1, 2 and 3, respectively, suggesting that pork prices increased by 1.1666 Korean won in regime 1 when ASF-related SNS frequencies increased. To promote pork consumption by SNS posts, the required SNS frequencies were estimated to have impacts as great as one standard deviation in the pork price. These values were 247.057, 1309.158 and 2817.266 for regimes 1, 2 and 3, respectively. The impact response periods for pork prices were estimated to last 48, 6, and 8 days for regimes 1, 2 and 3, respectively. When the prediction accuracies of the TAR and autoregressive (AR) models with regard to pork prices were compared for the root mean square error, the prediction accuracy of the TAR model was found to be slightly better than that of the AR. When the threshold effect of AI-related news on chicken prices was tested, a linear relationship appeared without a threshold effect. These findings suggest that when infectious diseases such as ASF occur for the first time, the impact on livestock prices is significant, as indicated by the threshold effect and the long impact response period. Our findings also suggest that the impact on livestock prices is not remarkable when infectious diseases occur multiple times, as in the case of AI. To date, this study is the first to suggest the use of SNS to promote meat consumption.

Parental knowledge and attitudes towards vaccination of children under 18 years of age

Background: Preventive vaccinations are the essence for the protection of humanity against the consequences of infectious diseases. They shape “herd” immunity if the entire population prevent disease incidence, morbidity. This ultimately reduces the number and severity of complications and death in the human population. Effective and active immunization of children and young people depends strongly on society’s level of knowledge about preventive vaccinations. Objectives: The study’s main objective was to evaluate the level of parental knowledge and attitudes towards preventive vaccinations in children and teens as well as the identification of factors determining the attitudes of parents towards the obligation to conduct preventive vaccinations in children and teens under 18 years of age. Material and methods: The research group consisted of 170 parents. A diagnostic survey and questionnaire technique was used with the use of the author’s original questionnaire. The survey questionnaire consisted of 27 questions. Results: Most parents had an average level of knowledge (n=136; 79.5%) about preventive vaccinations. It was noticed that the higher the level of parental knowledge about preventive vaccinations, the more often they deemed vaccinations necessary. The level of parental knowledge about preventive vaccinations does not depend on their age or education but rather their domicile location. Parental education, as well as domicile, did not significantly influence their attitudes towards the obligation of preventive vaccinations. Conclusions: Parental knowledge about preventive vaccinations is on an average level. The relation between the parents’ opinions about mandatory immunization in Poland and their knowledge in this field was not noticed. The level of parental knowledge about mandatory immunization was not statistically significant or dependent on age and education. More often than men, women claimed that the vaccination schedule effectively stabilizes and positively influences the epidemiological situation in Poland.

On the reproduction number and the optimal control of infectious diseases in a heterogenous population

The effect of infectious diseases cannot be overemphasised. The continuing surfacing of the infectious diseases gives the stakeholders a great concern. In this paper, the nature of the spread of Ebola virus outbreak in West Africa in 2014 is studied. We develop a model that analyses the spread of infectious diseases, and the reproduction number is determined by using the next generation matrix method. Finally, the effects of treatment of the infected individuals and vaccination of the susceptible population as the control strategies are looked into. The optimal control system showed that the combination of the two strategies proved more effective.

Evaluation of Boron's Adjuvant Activity in Inactive Bacterin Vaccines Using the Mice Model.

Vaccination is the most effective, reliable, and economical way of preventing or reducing the effect of infectious diseases. When preparing inactive vaccines, a range of additives called adjuvants are necessary to enhance the magnitude of the immune response. Boron has a wide range of industrial and medical applications, and its positive effects on distinct functions have been described in plants, humans, and animals. However, no studies exist about the possible adjuvant activities of boron compounds in vaccines. Hence, in this study, the potential adjuvant effect of boric acid was explored and compared with common veterinary adjuvants in a mice model. Staphylococcus aureus (S. aureus) used as vaccine antigen was isolated from dairy cows with bovine mastitis. Vaccines adjuvanted with boric acid, aluminum hydroxide, Montanide ISA 50 and ISA 206, and Montanide + boric acid combinations were prepared. The efficacy of vaccines was evaluated according to local reactions at the injection site, C-reactive protein, total Ig G, total Ig M, and anti-S. aureus antibody levels in mice. Boric acid reduced local inflammatory reactions induced by the Montanide adjuvants. Moreover, mice vaccinated with boric acid-adjuvanted vaccine had higher levels of anti-S. aureus antibody than those in the controls (P < 0.05) and were similar to the levels found in mice sensitized with aluminum hydroxide. Total Ig G and Ig M results were, however, unsuitable for the assessment of adjuvant activity for this study. In conclusion, this study revealed that boric acid has an adjuvant potential in inactive bacterin vaccines, but further target animal studies are needed.

Effects of 1, 25-dihydroxy vitamin D3 on clinical symptoms, pro-inflammatory and inflammatory cytokines in calves with experimental pneumonia

1, 25-dihydroxycholecalciferol is recognized as a potent immune-modulator which can fight against the pathogens via the activation of vitamin D3 receptors (VDRs), as well as stimulating various cytokines in infectious diseases. In the present study, because of the vitamin D3 has an appropriate immunomodulatory, the effects of this vitamin on the levels of pre-inflammatory and anti-inflammatory cytokines have been investigated in calves with experimental pasteurellosis. This study was experimentally carried out on 10 Holstein crossbred male calves (2–4 months) that were divided into two groups. Prepared Pasteurella multocida (3 × 109 CFU/mL) was inoculated in the trachea with a lavage catheter and then the treatment group was injected with 1, 25-dihydroxycholecalciferol after confirming pneumonia. Blood sampling, clinical symptoms scoring and radiological evaluation were recorded for both groups at different time intervals. The prescription of, vitamin D3 to the treatment group caused a decline in clinical symptoms score and changed interstitial and alveolo-interstitial lung pattern to such a degree that it could recover in comparison with the control group.The concentrations of pro-inflammatory cytokines (i.e., IL-1β, IL-6, and TNF-α) and the chemokine (IL-8) showed a significant decrease in the treatment group while the concentration of IL-10 increased in the treatment groups following the vitamin D3 injection (P = .001). The evidence from the current study suggests that vitamin D3 exert the immunomodulatory effects in infectious diseases through the regulation of cytokines and activation of VDR pathways to produce antimicrobial peptides.

Hyaluronic acid-based levofloxacin nanomicelles for nitric oxide-triggered drug delivery to treat bacterial infections.

Antibiotics are powerful weapons to fight against bacterial infections, while most of them lack of selective targeting towards pathological site which could restrict their antibacterial efficacy. To overcome this challenge, an antimicrobial levofloxacin(LF)was conjugated onto hyaluronic acid (HA) moieties via an o-phenylenediamine linker to prepare a NO-sensitive nanosystem (HA-NO-LF) in this study. The HA-NO-LF nanomicelles could enter host cells via a CD44 mediated endocytosis and release drug gradually upon exposure to endogenous NO. Furthermore, the more promising therapeutic effect of the nanomicelles in ameliorating inflammatory levels was observed in a mouse pneumonia model than that of LF. These results suggest that the HA-NO-LF nanomicelles may exert potent curative effect in infectious diseases.

Rh-IFN-α attenuates neuroinflammation and improves neurological function by inhibiting NF-κB through JAK1-STAT1/TRAF3 pathway in an experimental GMH rat model

Neuroinflammation occurs after germinal matrix hemorrhage (GMH) and induces secondary brain injury. Interferon-α (IFN-α) has been shown to exert anti-inflammatory effects in infectious diseases via activating IFNAR and its downstream signaling. We aimed to investigate the anti-inflammatory effects of Recombinant human IFN-α (rh-IFN-α) and the underlying mechanisms in a rat GMH model. Two hundred and eighteen P7 rat pups of both sexes were subjected to GMH by an intraparenchymal injection of bacterial collagenase. Rh-IFN-α was administered intraperitoneally. Small interfering RNA (siRNA) of IFNAR, and siRNA of tumor necrosis factor receptor associated factor 3 (TRAF3) were administered through intracerebroventricular (i.c.v.) injections. JAK1 inhibitor ruxolitinib was given by oral lavage. Post-GMH evaluation included neurobehavioral function, Nissl staining, Western blot analysis, and immunofluorescence. Our results showed that endogenous IFN-α and phosphorylated IFNAR levels were increased after GMH. Administration of rh-IFN-α improved neurological functions, attenuated neuroinflammation, inhibited microglial activation, and ameliorated post-hemorrhagic hydrocephalus after GMH. These observations were concomitant with IFNAR activation, increased expression of phosphorylated JAK1, phosphorylated STAT1 and TRAF3, and decreased levels of phosphorylated NF-κB, IL-6 and TNF-α. Specifically, knockdown of IFNAR, JAK1 and TRAF3 abolished the protective effects of rh-IFN-α. In conclusion, our findings demonstrated that rh-IFN-α treatment attenuated neuroinflammation, neurological deficits and hydrocephalus formation through inhibiting microglial activation after GMH, which might be mediated by IFNAR/JAK1-STAT1/TRAF3/NF-κB signaling pathway. Rh-IFN-α may be a promising therapeutic agent to attenuate brain injury via its anti-inflammatory effect.

The ameliorating effect of some immune-stimulants on bursal and tracheal lesions of broiler chickens challenged with ND virus

BackgroundNowadays, immuno-stimulants have great importance in improving the immune system and minimising the effect of infectious diseases in poultry flocks. This study was designed to demonstrate the impact of using different immune-stimulants on the reduction of the harmful implications of virulent ND virus through evaluation of histopathological lesion scores on bursa and trachea of vaccinated and infected broiler chickens with Newcastle disease (ND).ResultsEighty Ross breed broiler chicks at the age of 1 day were randomly divided into four groups, each group formed of 20 birds. Group I was vaccinated against AI, ND and IBD and used as a control. Groups II, III and IV were immunised as group I and also had immuno-stimulant supplement, Imutrix® (oregano oils plus ß-glucan), Evit liquid® (Vitamin E plus selenium) and Immunair 17.5 (Propionibacterium acnes and E. coli lipopolysaccharides), respectively. All groups were experimentally infected with virulent ND virus at the age of 28 days. The morbidity rates for groups I, II, III and IV were 15%, 5%, 5% and 10% respectively. Histopathological examination of bursa revealed hyperplasia of lymphoid follicles in group I which became more evident in groups II, III and IV. Group III showed hyperplasia of tracheal epithelium with lymphocytes and heterophils infiltration in lamina propria. CD79A-positive cells were significantly higher in bursa of group III in comparison to other groups during an immunohistochemical examination.ConclusionIt was concluded that Evit liquid® (vitamin E plus selenium) supplementation might have potent immunomodulatory effect in chickens.

Ureaplasma spp. lipid-associated membrane proteins induce human monocyte U937 cell cycle arrest through p53-independent p21 pathway

Ureaplasma spp. are known to be associated with human genitourinary tract diseases and perinatal diseases and Ureaplasma spp. Lipid-associated membrane proteins (LAMPs) play important roles in their related diseases. However, the exact mechanism underlying pathogenesis of Ureaplasma spp. LAMPs is largely unknown. In this study, we explored the pathogenic mechanisms of Ureaplasma spp. LAMPs by elucidating their role in modulating the cell cycle and related signaling pathways in human monocytic cell U937, which is highly related to the inflammatory and protective effect in infectious diseases. We utilized the two ATCC reference strains (Ureaplasma parvum serovar 3 str. ATCC 27,815 (UPA3) and Ureaplasma urealyticum serovar 8 str. ATCC 27,618 (UUR8)) and nine clinical isolates which including both UPA and UUR to study the effects of Ureaplasma spp. LAMPs on U937 in vitro. We found that LAMPs derived from UUR8 and both UPA and UUR of clinical strains markedly inhibited the cell proliferation, while UPA3 LAMPs suppressed slightly. Besides, the result of flow cytometry analysis indicated all the Ureaplasma spp. LAMPs could arrest U937 cells in G1 phase. Next, we found that the cell cycle arrest was associated with increased levels of p53 and p21, and a concomitant decrease in the levels of CDK2, CDK4, CDK6 and cyclin E1 at both transcriptional and translational levels after treatment with LAMPs derived from UUR8 or clinical strains, while only cyclin E1 was down-regulated after treatment with UPA3 LAMPs. Further study showed that p53 down-regulation had almost no effect on the distribution of cell cycle and the expression of p21. In conclusion, this study demonstrated that LAMPs derived from UUR8 and clinical strains could inhibit the proliferation of U937 cells by inducing G1 cell cycle arrest through increasing the p21 expression in a p53-independent manner, while UPA3 LAMPs could induce the cell cycle arrest slightly. Our study could contribute to the understanding of Ureaplasma spp. pathogenesis, which has potential value for the treatment of Ureaplasma spp. infections.

Hydroxysafflor Yellow A Attenuates the Apoptosis of Peripheral Blood CD4+ T Lymphocytes in a Murine Model of Sepsis.

Sepsis is generally considered as a severe condition of inflammation that leads to lymphocyte apoptosis and multiple organ dysfunction. Hydroxysafflor yellow A (HSYA) exerts anti-inflammatory and anti-apoptotic effects in infectious diseases. However, the therapeutic effect of HSYA on polymicrobial sepsis remains unknown. This study was undertaken to investigate the therapeutic effects and the mechanisms of action of HSYA on immunosuppression in a murine model of sepsis induced by cecal ligation and puncture (CLP). NIH mice were randomly divided into four groups: control group, sham group, CLP group, and CLP+HSYA group. HSYA (120 mg/kg) was intravenously injected into experimental mice at 12 h before CLP, concurrent with CLP and 12 h after CLP. The levels of circulating inflammatory cytokines, the apoptosis of CD4+ and CD8+ T lymphocytes, and protein expression of cytochrome C (Cytc), Bax, Bcl-2, cleaved caspase-9, and cleaved caspase-3 were examined. Plasma levels of IL-6, IL-10 and TNF-alpha as well as the apoptosis of CD4+ T lymphocytes were increased compared with sham group. These changes were accompanied by increases of pro-apoptotic proteins including Cytc, Bax, cleaved caspase-9, and cleaved caspase-3 and decreases of anti-apoptotic protein Bcl-2 in CD4+ T lymphocytes from mice undergoing CLP. In contrast, we fail to observe significant effect of HSYA on the apoptosis of CD8+ T lymphocytes in CLP-treated group. Of note, HSYA treatment reversed all above changes observed in CD4+ T lymphocytes, and significantly increased the ratio of CD4+:CD8+ T lymphocytes in CLP-treated mice. In conclusion, HSYA was an effective therapeutic agent in ameliorating sepsis-induced apoptosis of CD4+ T lymphocytes probably through its anti-inflammatory and anti-apoptotic effects.